chr5-180590788-C-T

Variant names:

• chr5-180590788-C-T
• NM_052863.3:c.103G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_052863.3(SCGB3A1):​c.103G>A​(p.Ala35Thr) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A35E) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SCGB3A1 NM_052863.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.796
• Publications: 0 publications found

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]

ENSG00000307523 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052094012).

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.103G>A	p.Ala35Thr	missense	Exon 2 of 3	NP_443095.2	Q96QR1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCGB3A1	ENST00000292641.4	TSL:1 MANE Select	c.103G>A	p.Ala35Thr	missense	Exon 2 of 3	ENSP00000292641.3	Q96QR1
	SCGB3A1	ENST00000899434.1		c.103G>A	p.Ala35Thr	missense	Exon 2 of 3	ENSP00000569493.1
	SCGB3A1	ENST00000512120.1	TSL:2	n.376G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1447500 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 718872

African (AFR) AF: 0.00 AC: 0 AN: 33074

American (AMR) AF: 0.00 AC: 0 AN: 43094

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25792

East Asian (EAS) AF: 0.00 AC: 0 AN: 38754

South Asian (SAS) AF: 0.00 AC: 0 AN: 83864

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51830

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105690

Other (OTH) AF: 0.00 AC: 0 AN: 59712

GnomAD4 genome Cov.: 33

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	0.084
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.061	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.80
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.025
Sift	Benign	0.25	T
Sift4G	Benign	0.26	T
Polyphen		0.019	B
Vest4		0.061
MutPred		0.23		Gain of glycosylation at A35 (P = 0.0317)
MVP		0.055
MPC		0.63
ClinPred		0.10	T
GERP RS		0.43
Varity_R		0.099
gMVP		0.092
Mutation Taster		=100/0	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

hg19: chr5-180017788;