6-31412017-C-G

Position:

• chr6-31412017-C-G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001177519.3(MICA):​c.684C>G​(p.Ser228=) 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MICA NM_001177519.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.49

Genes affected

MICA (HGNC:7090): (MHC class I polypeptide-related sequence A) This gene encodes the highly polymorphic major histocompatability complex class I chain-related protein A. The protein product is expressed on the cell surface, although unlike canonical class I molecules it does not seem to associate with beta-2-microglobulin. It is a ligand for the NKG2-D type II integral membrane protein receptor. The protein functions as a stress-induced antigen that is broadly recognized by intestinal epithelial gamma delta T cells. Variations in this gene have been associated with susceptibility to psoriasis 1 and psoriatic arthritis, and the shedding of MICA-related antibodies and ligands is involved in the progression from monoclonal gammopathy of undetermined significance to multiple myeloma. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 6-31412017-C-G is Benign according to our data. Variant chr6-31412017-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3257563.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.49 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MICA	NM_001177519.3	c.684C>G	p.Ser228=	synonymous_variant	4/6	ENST00000449934.7	NP_001170990.1
MICA	NM_001289152.2	c.393C>G	p.Ser131=	synonymous_variant	4/6		NP_001276081.1
MICA	NM_001289153.2	c.393C>G	p.Ser131=	synonymous_variant	4/6		NP_001276082.1
MICA	NM_001289154.2	c.270C>G	p.Ser90=	synonymous_variant	4/6		NP_001276083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MICA	ENST00000449934.7	c.684C>G	p.Ser228=	synonymous_variant	4/6	1	NM_001177519.3	ENSP00000413079	P1
MICA	ENST00000616296.4	c.393C>G	p.Ser131=	synonymous_variant	4/6	5		ENSP00000482382
MICA	ENST00000421350.1	c.357C>G	p.Ser119=	synonymous_variant	3/5	5		ENSP00000402410
MICA	ENST00000674069.1	c.270C>G	p.Ser90=	synonymous_variant	4/6			ENSP00000501157

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 51

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

MICA: PM2:Supporting, BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.28
DANN	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs1051797; hg19: chr6-31379794;