rs768171462

Variant names:

• chrX-11760863-G-A
• rs768171462
• NM_078629.4:c.308G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-11760863-G-A
• chrX-11760863-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_078629.4(MSL3):​c.308G>A​(p.Arg103His) variant causes a missense change. The variant allele was found at a frequency of 0.00000553 in 1,085,228 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000055 (0 hom. 1 hem.)
• Consequence: MSL3 NM_078629.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.89
• Publications: 2 publications found

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]

MSL3 Gene-Disease associations (from GenCC):

• Basilicata-Akhtar syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21203443).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_078629.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSL3	NM_078629.4	MANE Select	c.308G>A	p.Arg103His	missense	Exon 4 of 13	NP_523353.2	Q8N5Y2-1
	MSL3	NM_001193270.2		c.272G>A	p.Arg91His	missense	Exon 4 of 13	NP_001180199.1	Q8N5Y2-3
	MSL3	NM_078628.2		c.308G>A	p.Arg103His	missense	Exon 4 of 9	NP_523352.1	Q8N5Y2-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSL3	ENST00000312196.10	TSL:1 MANE Select	c.308G>A	p.Arg103His	missense	Exon 4 of 13	ENSP00000312244.4	Q8N5Y2-1
	MSL3	ENST00000647869.1		c.308G>A	p.Arg103His	missense	Exon 4 of 13	ENSP00000497615.1	A0A3B3IT59
	MSL3	ENST00000398527.7	TSL:2	c.272G>A	p.Arg91His	missense	Exon 4 of 13	ENSP00000381538.2	Q8N5Y2-3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000188 AC: 3 AN: 159867 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000244

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000553 AC: 6 AN: 1085228 Hom.: 0 Cov.: 28 AF XY: 0.00000283 AC XY: 1 AN XY: 352876

African (AFR) AF: 0.00 AC: 0 AN: 26016

American (AMR) AF: 0.00 AC: 0 AN: 33755

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19040

East Asian (EAS) AF: 0.0000671 AC: 2 AN: 29812

South Asian (SAS) AF: 0.00 AC: 0 AN: 51429

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40068

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4116

European-Non Finnish (NFE) AF: 0.00000479 AC: 4 AN: 835434

Other (OTH) AF: 0.00 AC: 0 AN: 45558

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Basilicata-Akhtar syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.055	T
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.84	T
M_CAP	Pathogenic	0.49	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		5.9
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.20
Sift	Benign	0.055	T
Sift4G	Benign	0.13	T
Polyphen		1.0	D
Vest4		0.17
MutPred		0.34		Loss of MoRF binding (P = 0.0671)
MVP		0.65
MPC		0.77
ClinPred		0.36	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.43
gMVP		0.44
Mutation Taster		=199/101	polymorphism

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

Other links and lift over

dbSNP: rs768171462; hg19: chrX-11778982; COSMIC: COSV56495497; COSMIC: COSV56495497;