rs11754464

chr6-31755958-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_172166.4(MSH5):c.1015-2207C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00509 in 151,154 control chromosomes in the GnomAD database, including 5 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 0.0051 (5 hom., cov: 32)
• Consequence: MSH5 NM_172166.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSH5	NM_172166.4	c.1015-2207C>T		intron_variant		ENST00000375750.9
MSH5-SAPCD1	NR_037846.1	n.1194-2207C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSH5	ENST00000375750.9	c.1015-2207C>T		intron_variant		1	NM_172166.4	A2

Frequencies

GnomAD3 genomes AF: 0.00509 AC: 769 AN: 151062 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.000777

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00692

Gnomad ASJ AF: 0.0361

Gnomad EAS AF: 0.0152

Gnomad SAS AF: 0.0135

Gnomad FIN AF: 0.000398

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.00494

Gnomad OTH AF: 0.00818

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

GnomAD4 genome AF: 0.00509 AC: 769 AN: 151154 Hom.: 5 Cov.: 32 AF XY: 0.00556 AC XY: 410 AN XY: 73796

Gnomad4 AFR AF: 0.000775

Gnomad4 AMR AF: 0.00691

Gnomad4 ASJ AF: 0.0361

Gnomad4 EAS AF: 0.0153

Gnomad4 SAS AF: 0.0135

Gnomad4 FIN AF: 0.000398

Gnomad4 NFE AF: 0.00494

Gnomad4 OTH AF: 0.00811

Alfa AF: 0.00735 Hom.: 14

Bravo AF: 0.00524

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	7.3
Dann	Benign	0.77

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: rs11754464; hg19: chr6-31723735;