Genetic Variant SCGB3A1:p.Val87Met (chr5-180590632-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_052863.3(SCGB3A1):c.259G>A(p.Val87Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000624 in 1,602,100 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000041 ( 1 hom. )

Consequence

SCGB3A1
NM_052863.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.04

Publications

1 publications found

Variant links:

Genes affected

SCGB3A1 (HGNC:18384): (secretoglobin family 3A member 1) Predicted to be involved in positive regulation of myoblast fusion. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

SCGB3A1 links:

ENSG00000307523 (HGNC:):

ENSG00000307523 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.020914495).

BP6

Variant 5-180590632-C-T is Benign according to our data. Variant chr5-180590632-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3438017.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052863.3. 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
	SCGB3A1	NM_052863.3	MANE Select	c.259G>A	p.Val87Met	missense	Exon 2 of 3	NP_443095.2	Q96QR1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCGB3A1	ENST00000292641.4	TSL:1 MANE Select	c.259G>A	p.Val87Met	missense	Exon 2 of 3	ENSP00000292641.3	Q96QR1
SCGB3A1	ENST00000899434.1		c.259G>A	p.Val87Met	missense	Exon 2 of 3	ENSP00000569493.1
SCGB3A1	ENST00000512120.1	TSL:2	n.532G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

220912

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000414

AC:

AN:

1449776

Hom.:

Cov.:

AF XY:

0.00000555

AC XY:

AN XY:

720172

show subpopulations

African (AFR)

AF:

0.000151

AC:

AN:

33152

American (AMR)

AF:

0.00

AC:

AN:

43402

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25770

East Asian (EAS)

AF:

0.00

AC:

AN:

39034

South Asian (SAS)

AF:

0.0000119

AC:

AN:

84064

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52242

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106630

Other (OTH)

AF:

0.00

AC:

AN:

59768

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.0000962

AC:

AN:

41576

American (AMR)

AF:

0.00

AC:

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2112

Alfa

AF:

0.000789

Hom.:

ExAC

AF:

0.00000828

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.0

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.023

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0049

LIST_S2

Benign

0.31

M_CAP

Benign

0.0070

MetaRNN

Benign

0.021

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.58

PhyloP100

-3.0

PrimateAI

Benign

0.27

PROVEAN

Benign

0.54

REVEL

Benign

0.021

Sift

Benign

0.17

Sift4G

Benign

0.23

Polyphen

0.011

Vest4

0.15

MutPred

0.14

Gain of helix (P = 0.0696)

MVP

0.030

MPC

0.72

ClinPred

0.11

GERP RS

-6.3

Varity_R

0.033

gMVP

0.22

Mutation Taster

=99/1

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over