rs1457968907

Variant names:

• chr7-29936598-G-A
• rs1457968907
• NM_014766.5:c.863C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-29936598-G-A
• chr7-29936598-G-T

Variant summary

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

The NM_014766.5(SCRN1):​c.863C>T​(p.Ser288Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S288Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SCRN1 NM_014766.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 1 publications found

Genes affected

SCRN1 (HGNC:22192): (secernin 1) This gene likely encodes a member of the secernin family of proteins. A similar protein in rat functions in regulation of exocytosis in mast cells. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2009]

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=0.08880484).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014766.5. 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
	SCRN1	NM_014766.5	MANE Select	c.863C>T	p.Ser288Phe	missense	Exon 6 of 8	NP_055581.3
	SCRN1	NM_001145514.1		c.923C>T	p.Ser308Phe	missense	Exon 6 of 8	NP_001138986.1	Q12765-2
	SCRN1	NM_001145513.1		c.863C>T	p.Ser288Phe	missense	Exon 6 of 8	NP_001138985.1	Q12765-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCRN1	ENST00000242059.10	TSL:1 MANE Select	c.863C>T	p.Ser288Phe	missense	Exon 6 of 8	ENSP00000242059.5	Q12765-1
	SCRN1	ENST00000434476.6	TSL:2	c.923C>T	p.Ser308Phe	missense	Exon 6 of 8	ENSP00000388942.1	Q12765-2
	SCRN1	ENST00000409497.5	TSL:2	c.863C>T	p.Ser288Phe	missense	Exon 5 of 7	ENSP00000386872.1	Q12765-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250420 AF XY: 0.00000739

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: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450840 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 719860

African (AFR) AF: 0.00 AC: 0 AN: 33358

American (AMR) AF: 0.00 AC: 0 AN: 44482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25988

East Asian (EAS) AF: 0.00 AC: 0 AN: 39368

South Asian (SAS) AF: 0.00 AC: 0 AN: 85198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1103488

Other (OTH) AF: 0.00 AC: 0 AN: 59940

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.3
DANN	Benign	0.76
DEOGEN2	Benign	0.0036	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.080	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.1
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.042
Sift	Benign	0.078	T
Sift4G	Uncertain	0.054	T
Polyphen		0.0	B
Vest4		0.28
MutPred		0.29		Loss of disorder (P = 0.0225)
MVP		0.095
MPC		0.24
ClinPred		0.017	T
GERP RS		0.11
Varity_R		0.022
gMVP		0.67
Mutation Taster		=92/8	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: rs1457968907; hg19: chr7-29976214;