4-70366981-C-T

Variant names:

• chr4-70366981-C-T
• rs1732282499
• NM_012390.4:c.392C>T

Variant summary

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

The NM_012390.4(SMR3A):​c.392C>T​(p.Thr131Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,460,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: SMR3A NM_012390.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0740
• Publications: 0 publications found

Genes affected

SMR3A (HGNC:19216): (submaxillary gland androgen regulated protein 3A) Predicted to enable endopeptidase inhibitor activity. Predicted to be involved in regulation of sensory perception of pain. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

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=0.08818331).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012390.4. 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
	SMR3A	NM_012390.4	MANE Select	c.392C>T	p.Thr131Ile	missense	Exon 3 of 3	NP_036522.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMR3A	ENST00000226460.5	TSL:1 MANE Select	c.392C>T	p.Thr131Ile	missense	Exon 3 of 3	ENSP00000226460.4	Q99954

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1460626 Hom.: 0 Cov.: 75 AF XY: 0.0000138 AC XY: 10 AN XY: 726612

African (AFR) AF: 0.00 AC: 0 AN: 33418

American (AMR) AF: 0.00 AC: 0 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26054

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39680

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00000990 AC: 11 AN: 1111258

Other (OTH) AF: 0.00 AC: 0 AN: 60334

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000313 Hom.: 0

EpiCase AF: 0.0000546

EpiControl AF: 0.00

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	0.14
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.0
DANN	Benign	0.40
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.074
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.0040
Sift	Benign	0.049	D
Sift4G	Benign	0.15	T
Polyphen		0.026	B
Vest4		0.055
MVP		0.014
MPC		0.065
ClinPred		0.039	T
GERP RS		-0.63
Varity_R		0.037
gMVP		0.11
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

dbSNP: rs1732282499; hg19: chr4-71232698;