rs142178082

Variant names:

• chr17-76057461-A-G
• rs142178082
• NM_014230.4:c.920T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-76057461-A-G
• chr17-76057461-A-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.920T>C​(p.Ile307Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: SRP68 NM_014230.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.82
• 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]

SRP68 Gene-Disease associations (from GenCC):

• neutropenia, severe congenital, 10, autosomal recessive

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, PanelApp Australia

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=0.2630635).

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.920T>C	p.Ile307Thr	missense	Exon 8 of 16	NP_055045.2
	SRP68	NM_001260502.2		c.806T>C	p.Ile269Thr	missense	Exon 7 of 15	NP_001247431.1	Q9UHB9-4
	SRP68	NR_048541.2		n.842T>C		non_coding_transcript_exon	Exon 7 of 15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRP68	ENST00000307877.7	TSL:1 MANE Select	c.920T>C	p.Ile307Thr	missense	Exon 8 of 16	ENSP00000312066.1	Q9UHB9-1
	SRP68	ENST00000936368.1		c.920T>C	p.Ile307Thr	missense	Exon 8 of 16	ENSP00000606427.1
	SRP68	ENST00000909201.1		c.920T>C	p.Ile307Thr	missense	Exon 8 of 16	ENSP00000579260.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251480 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461884 Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000629 AC: 7 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

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	0.14
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.2	L
PhyloP100		8.8
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	0.24	N
REVEL	Benign	0.18
Sift	Benign	0.23	T
Sift4G	Benign	0.39	T
Polyphen		0.59	P
Vest4		0.57
MVP		0.22
MPC		0.85
ClinPred		0.51	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.42
Mutation Taster		=13/87	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs142178082; hg19: chr17-74053542;