rs3130484

Positions:

• chr6-31748105-T-C

Variant summary

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

The NM_172166.4(MSH5):​c.812+673T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0766 in 152,184 control chromosomes in the GnomAD database, including 561 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 0.077 (561 hom., cov: 31)
• Consequence: MSH5 NM_172166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

Genes affected

MSH5 (HGNC:7328): (mutS homolog 5) This gene encodes a member of the mutS family of proteins that are involved in DNA mismatch repair and meiotic recombination. This protein is similar to a Saccharomyces cerevisiae protein that participates in segregation fidelity and crossing-over events during meiosis. This protein plays a role in promoting ionizing radiation-induced apoptosis. This protein forms hetero-oligomers with another member of this family, mutS homolog 4. Polymorphisms in this gene have been linked to various human diseases, including IgA deficiency, common variable immunodeficiency, and premature ovarian failure. Alternative splicing results multiple transcript variants. Read-through transcription also exists between this gene and the downstream chromosome 6 open reading frame 26 (C6orf26) gene. [provided by RefSeq, Feb 2011]

MSH5-SAPCD1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSH5	NM_172166.4	c.812+673T>C		intron_variant		ENST00000375750.9	NP_751898.1
MSH5-SAPCD1	NR_037846.1	n.991+673T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSH5	ENST00000375750.9	c.812+673T>C		intron_variant		1	NM_172166.4	ENSP00000364903	A2

Frequencies

GnomAD3 genomes AF: 0.0767 AC: 11663 AN: 152066 Hom.: 561 Cov.: 31

Gnomad AFR AF: 0.0627

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0373

Gnomad ASJ AF: 0.0398

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0789

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0585

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

GnomAD4 genome AF: 0.0766 AC: 11664 AN: 152184 Hom.: 561 Cov.: 31 AF XY: 0.0713 AC XY: 5305 AN XY: 74404

Gnomad4 AFR AF: 0.0626

Gnomad4 AMR AF: 0.0371

Gnomad4 ASJ AF: 0.0398

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0789

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.0579

Alfa AF: 0.0925 Hom.: 648

Bravo AF: 0.0733

Asia WGS AF: 0.00837 AC: 30 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3130484; hg19: chr6-31715882;