NM_014766.5:c.925A>G

Variant names:

• chr7-29926613-T-C
• rs151249549
• NM_014766.5:c.925A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_014766.5(SCRN1):​c.925A>G​(p.Ile309Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 1,613,958 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (7 hom.)
• Consequence: SCRN1 NM_014766.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.39
• Publications: 7 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.017178923).
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

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.925A>G	p.Ile309Val	missense	Exon 7 of 8	NP_055581.3
	SCRN1	NM_001145514.1		c.985A>G	p.Ile329Val	missense	Exon 7 of 8	NP_001138986.1	Q12765-2
	SCRN1	NM_001145513.1		c.925A>G	p.Ile309Val	missense	Exon 7 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.925A>G	p.Ile309Val	missense	Exon 7 of 8	ENSP00000242059.5	Q12765-1
	SCRN1	ENST00000434476.6	TSL:2	c.985A>G	p.Ile329Val	missense	Exon 7 of 8	ENSP00000388942.1	Q12765-2
	SCRN1	ENST00000409497.5	TSL:2	c.925A>G	p.Ile309Val	missense	Exon 6 of 7	ENSP00000386872.1	Q12765-1

Frequencies

GnomAD3 genomes AF: 0.00125 AC: 190 AN: 152060 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000387

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00194

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00117 AC: 293 AN: 251398 AF XY: 0.00112

Gnomad AFR exome AF: 0.000615

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.00189

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000323

Gnomad NFE exome AF: 0.00179

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.00167 AC: 2438 AN: 1461780 Hom.: 7 Cov.: 32 AF XY: 0.00163 AC XY: 1186 AN XY: 727192

African (AFR) AF: 0.000239 AC: 8 AN: 33470

American (AMR) AF: 0.00143 AC: 64 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00203 AC: 53 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.000412 AC: 22 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00198 AC: 2203 AN: 1111952

Other (OTH) AF: 0.00146 AC: 88 AN: 60394

GnomAD4 genome AF: 0.00125 AC: 190 AN: 152178 Hom.: 1 Cov.: 32 AF XY: 0.00118 AC XY: 88 AN XY: 74392

African (AFR) AF: 0.000385 AC: 16 AN: 41516

American (AMR) AF: 0.00177 AC: 27 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00194 AC: 132 AN: 68016

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.00168 Hom.: 0

Bravo AF: 0.00131

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00259 AC: 10

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00140 AC: 12

ExAC AF: 0.00121 AC: 147

EpiCase AF: 0.00196

EpiControl AF: 0.00166

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	0.10
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0042	T
Eigen	Benign	0.0046
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.70	N
PhyloP100		3.4
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.071
Sift	Benign	0.15	T
Sift4G	Benign	0.26	T
Polyphen		0.0030	B
Vest4		0.12
MVP		0.048
MPC		0.20
ClinPred		0.019	T
GERP RS		5.7
Varity_R		0.075
gMVP		0.57
Mutation Taster		=99/1	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: rs151249549; hg19: chr7-29966229; COSMIC: COSV54128401;