rs3735823

Positions:

• chr8-10075725-G-A
• chr8-10075725-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012331.5(MSRA):​c.142+21067G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 152,064 control chromosomes in the GnomAD database, including 22,955 homozygotes. 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: 𝑓 0.52 (22955 hom., cov: 33)
• Consequence: MSRA NM_012331.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.897

Genes affected

MSRA (HGNC:7377): (methionine sulfoxide reductase A) This gene encodes a ubiquitous and highly conserved protein that carries out the enzymatic reduction of methionine sulfoxide to methionine. Human and animal studies have shown the highest levels of expression in kidney and nervous tissue. The protein functions in the repair of oxidatively damaged proteins to restore biological activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSRA	NM_012331.5	c.142+21067G>A		intron_variant		ENST00000317173.9	NP_036463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSRA	ENST00000317173.9	c.142+21067G>A		intron_variant		1	NM_012331.5	ENSP00000313921	P1
MSRA	ENST00000441698.6	c.142+21067G>A		intron_variant		2		ENSP00000410912
MSRA	ENST00000518255.5	c.142+21067G>A		intron_variant		5		ENSP00000429461
MSRA	ENST00000521209.6	c.-57+16626G>A		intron_variant		3		ENSP00000435644

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79580 AN: 151946 Hom.: 22970 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.577

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.523 AC: 79550 AN: 152064 Hom.: 22955 Cov.: 33 AF XY: 0.525 AC XY: 38998 AN XY: 74340

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.560

Gnomad4 ASJ AF: 0.701

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.648

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.569

Alfa AF: 0.574 Hom.: 5493

Bravo AF: 0.508

Asia WGS AF: 0.463 AC: 1611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.7
DANN	Benign	0.52

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: rs3735823; hg19: chr8-9933235;