chr5-180590242-C-T

Variant names:

• chr5-180590242-C-T
• NM_052863.3:c.304G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_052863.3(SCGB3A1):​c.304G>A​(p.Val102Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SCGB3A1 NM_052863.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.31

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.018768162).
• BP6: Variant 5-180590242-C-T is Benign according to our data. Variant chr5-180590242-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3438019.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCGB3A1	NM_052863.3	c.304G>A	p.Val102Met	missense_variant	Exon 3 of 3	ENST00000292641.4	NP_443095.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCGB3A1	ENST00000292641.4	c.304G>A	p.Val102Met	missense_variant	Exon 3 of 3	1	NM_052863.3	ENSP00000292641.3
SCGB3A1	ENST00000512120.1	n.577G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 24, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.11
DANN	Benign	0.12
DEOGEN2	Benign	0.024	T
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.0082	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.0	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.73	N
REVEL	Benign	0.012
Sift	Benign	1.0	T
Sift4G	Benign	0.64	T
Polyphen		0.0	B
Vest4		0.066
MutPred		0.22		Gain of disorder (P = 0.0575);
MVP		0.030
MPC		0.25
ClinPred		0.030	T
GERP RS		-8.8
Varity_R		0.021
gMVP		0.062

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-180017242;