NM_012390.4:c.228C>A

Variant names:

• chr4-70366817-C-A
• rs1224618081
• NM_012390.4:c.228C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_012390.4(SMR3A):​c.228C>A​(p.Ile76Ile) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SMR3A NM_012390.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=-1.44 with no splicing effect.

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.228C>A	p.Ile76Ile	synonymous	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.228C>A	p.Ile76Ile	synonymous	Exon 3 of 3	ENSP00000226460.4	Q99954

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 75

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.14
DANN	Benign	0.45
PhyloP100		-1.4

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: rs1224618081; hg19: chr4-71232534;