rs772627075

Variant names:

• chrX-11760438-G-A
• rs772627075
• NM_078629.4:c.221G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-11760438-G-A
• chrX-11760438-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001282174.1(MSL3):​c.-144G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,090,350 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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: not found (cov: 24)
  • Exomes 𝑓: 0.0000028 (0 hom. 0 hem.)
• Consequence: MSL3 NM_001282174.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24846852).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282174.1. 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.221G>A	p.Arg74His	missense	Exon 3 of 13	NP_523353.2	Q8N5Y2-1
	MSL3	NM_001282174.1		c.-144G>A		5_prime_UTR_premature_start_codon_gain	Exon 3 of 12	NP_001269103.1	Q8N5Y2-6
	MSL3	NM_006800.4		c.-278G>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 12	NP_006791.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSL3	ENST00000312196.10	TSL:1 MANE Select	c.221G>A	p.Arg74His	missense	Exon 3 of 13	ENSP00000312244.4	Q8N5Y2-1
	MSL3	ENST00000361672.6	TSL:2	c.-144G>A		5_prime_UTR_premature_start_codon_gain	Exon 3 of 12	ENSP00000354562.2	Q8N5Y2-6
	MSL3	ENST00000649685.1		c.-144G>A		5_prime_UTR_premature_start_codon_gain	Exon 3 of 12	ENSP00000497496.1	Q8N5Y2-6

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000275 AC: 3 AN: 1090350 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 357514

African (AFR) AF: 0.00 AC: 0 AN: 26214

American (AMR) AF: 0.0000291 AC: 1 AN: 34337

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19244

East Asian (EAS) AF: 0.00 AC: 0 AN: 29875

South Asian (SAS) AF: 0.00 AC: 0 AN: 52357

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40323

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3397

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 838889

Other (OTH) AF: 0.00 AC: 0 AN: 45714

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.5
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.095
Sift	Benign	0.13	T
Sift4G	Uncertain	0.043	D
Polyphen		0.0030	B
Vest4		0.14
MutPred		0.62		Loss of MoRF binding (P = 0.0176)
MVP		0.44
MPC		0.78
ClinPred		0.56	D
GERP RS		1.8
PromoterAI		-0.042	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.28
gMVP		0.68
Mutation Taster		=68/32	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs772627075; hg19: chrX-11778557; COSMIC: COSV105888274; COSMIC: COSV105888274;