rs754741659

Variant names:

• chr17-76072415-C-A
• rs754741659
• NM_014230.4:c.77G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-76072415-C-A
• chr17-76072415-C-G
• chr17-76072415-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014230.4(SRP68):​c.77G>T​(p.Gly26Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000114 in 1,584,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G26C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: SRP68 NM_014230.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.217
• Publications: 0 publications found

Genes affected

SRP68 (HGNC:11302): (signal recognition particle 68) This gene encodes a subunit of the signal recognition particle (SRP). The SRP is a ribonucleoprotein complex that transports secreted and membrane proteins to the endoplasmic reticulum for processing. The complex includes a 7S RNA and six protein subunits. The encoded protein is the 68kDa component of the SRP, and forms a heterodimer with the 72kDa subunit that is required for SRP function. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and three pseudogenes of this gene are located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, May 2012]

GALR2 (HGNC:4133): (galanin receptor 2) Galanin is an important neuromodulator present in the brain, gastrointestinal system, and hypothalamopituitary axis. It is a 30-amino acid non-C-terminally amidated peptide that potently stimulates growth hormone secretion, inhibits cardiac vagal slowing of heart rate, abolishes sinus arrhythmia, and inhibits postprandial gastrointestinal motility. The actions of galanin are mediated through interaction with specific membrane receptors that are members of the 7-transmembrane family of G protein-coupled receptors. GALR2 interacts with the N-terminal residues of the galanin peptide. The primary signaling mechanism for GALR2 is through the phospholipase C/protein kinase C pathway (via Gq), in contrast to GALR1, which communicates its intracellular signal by inhibition of adenylyl cyclase through Gi. However, it has been demonstrated that GALR2 couples efficiently to both the Gq and Gi proteins to simultaneously activate 2 independent signal transduction pathways. [provided by RefSeq, Jul 2008]

ZACN (HGNC:29504): (zinc activated ion channel) LGICZ1 is a zinc-activated ligand-gated ion channel that defines a new subgroup of the cysteine-loop superfamily of ligand-gated ion channels (Davies et al., 2003 [PubMed 12381728]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15206155).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014230.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRP68	NM_014230.4	MANE Select	c.77G>T	p.Gly26Val	missense	Exon 1 of 16	NP_055045.2
	SRP68	NM_001260502.2		c.77G>T	p.Gly26Val	missense	Exon 1 of 15	NP_001247431.1	Q9UHB9-4
	SRP68	NR_048541.2		n.103G>T		non_coding_transcript_exon	Exon 1 of 15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRP68	ENST00000307877.7	TSL:1 MANE Select	c.77G>T	p.Gly26Val	missense	Exon 1 of 16	ENSP00000312066.1	Q9UHB9-1
	SRP68	ENST00000936368.1		c.77G>T	p.Gly26Val	missense	Exon 1 of 16	ENSP00000606427.1
	SRP68	ENST00000909201.1		c.77G>T	p.Gly26Val	missense	Exon 1 of 16	ENSP00000579260.1

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151422 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000443

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000133 AC: 3 AN: 224886 AF XY: 0.0000159

Gnomad AFR exome AF: 0.0000756

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000197

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000105 AC: 15 AN: 1433500 Hom.: 0 Cov.: 32 AF XY: 0.00000981 AC XY: 7 AN XY: 713536

African (AFR) AF: 0.0000307 AC: 1 AN: 32556

American (AMR) AF: 0.00 AC: 0 AN: 44372

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25880

East Asian (EAS) AF: 0.00 AC: 0 AN: 39390

South Asian (SAS) AF: 0.00 AC: 0 AN: 85724

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 0.0000118 AC: 13 AN: 1099828

Other (OTH) AF: 0.0000168 AC: 1 AN: 59476

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151422 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 73978

African (AFR) AF: 0.00 AC: 0 AN: 41106

American (AMR) AF: 0.00 AC: 0 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000443 AC: 3 AN: 67714

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000174 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.69	T
M_CAP	Pathogenic	0.35	D
MetaRNN	Benign	0.15	T
MetaSVM	Uncertain	0.40	D
MutationAssessor	Benign	0.69	N
PhyloP100		0.22
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.28
Sift	Benign	0.048	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.028	B
Vest4		0.28
MutPred		0.32		Loss of loop (P = 0.0603)
MVP		0.82
MPC		0.82
ClinPred		0.050	T
GERP RS		2.8
PromoterAI		0.024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.071
gMVP		0.74
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs754741659; hg19: chr17-74068496;