X-11761513-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_078629.4(MSL3):c.396C>T(p.Ser132=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00532 in 1,196,392 control chromosomes in the GnomAD database, including 205 homozygotes. There are 1,694 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (104 hom., 840 hem., cov: 24)
  • Exomes 𝑓: 0.0030 (101 hom. 854 hem.)
• Consequence: MSL3 NM_078629.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.43

Genes affected

MSL3 (HGNC:7370): (MSL complex subunit 3) This gene encodes a nuclear protein that is similar to the product of the Drosophila male-specific lethal-3 gene. The Drosophila protein plays a critical role in a dosage-compensation pathway, which equalizes X-linked gene expression in males and females. Thus, the human protein is thought to play a similar function in chromatin remodeling and transcriptional regulation, and it has been found as part of a complex that is responsible for histone H4 lysine-16 acetylation. This gene can undergo X inactivation. Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 2, 7 and 8. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant X-11761513-C-T is Benign according to our data. Variant chrX-11761513-C-T is described in ClinVar as [Benign]. Clinvar id is 3041463.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.43 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSL3	NM_078629.4	c.396C>T	p.Ser132=	synonymous_variant	5/13	ENST00000312196.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSL3	ENST00000312196.10	c.396C>T	p.Ser132=	synonymous_variant	5/13	1	NM_078629.4	P4

Frequencies

GnomAD3 genomes AF: 0.0273 AC: 3056 AN: 111934 Hom.: 103 Cov.: 24 AF XY: 0.0245 AC XY: 838 AN XY: 34144

Gnomad AFR AF: 0.0943

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000734

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00837

Gnomad NFE AF: 0.000207

Gnomad OTH AF: 0.0232

GnomAD3 exomes AF: 0.00833 AC: 1425 AN: 171162 Hom.: 50 AF XY: 0.00503 AC XY: 288 AN XY: 57200

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.00461

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000409

Gnomad OTH exome AF: 0.00383

GnomAD4 exome AF: 0.00304 AC: 3298 AN: 1084407 Hom.: 101 Cov.: 25 AF XY: 0.00243 AC XY: 854 AN XY: 351767

Gnomad4 AFR exome AF: 0.0998

Gnomad4 AMR exome AF: 0.00646

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000174

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000193

Gnomad4 OTH exome AF: 0.00676

GnomAD4 genome AF: 0.0273 AC: 3061 AN: 111985 Hom.: 104 Cov.: 24 AF XY: 0.0246 AC XY: 840 AN XY: 34205

Gnomad4 AFR AF: 0.0943

Gnomad4 AMR AF: 0.0109

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000737

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000207

Gnomad4 OTH AF: 0.0229

Alfa AF: 0.00913 Hom.: 78

Bravo AF: 0.0314

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

MSL3-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 22, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	12
Dann	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs78624542; hg19: chrX-11779632;