17-40129502-C-G

Variant names:

• chr17-40129502-C-G
• NM_001365919.1:c.1250C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001365919.1(MSL1):​c.1250C>G​(p.Ser417*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MSL1 NM_001365919.1 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

Genes affected

MSL1 (HGNC:27905): (MSL complex subunit 1) Predicted to enable chromatin binding activity. Involved in histone H4-K16 acetylation. Located in nucleoplasm. Part of MSL complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSL1	NM_001365919.1	c.1250C>G	p.Ser417*	stop_gained	Exon 3 of 9	ENST00000398532.9	NP_001352848.1
MSL1	NM_001365920.1	c.1250C>G	p.Ser417*	stop_gained	Exon 3 of 8		NP_001352849.1
MSL1	NM_001365921.2	c.1250C>G	p.Ser417*	stop_gained	Exon 3 of 3		NP_001352850.1
MSL1	NM_001012241.2	c.461C>G	p.Ser154*	stop_gained	Exon 4 of 10		NP_001012241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSL1	ENST00000398532.9	c.1250C>G	p.Ser417*	stop_gained	Exon 3 of 9	1	NM_001365919.1	ENSP00000381543.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.51	D
BayesDel_noAF	Pathogenic	0.50
CADD	Pathogenic	38
DANN	Uncertain	0.99
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Uncertain	0.90	D
Vest4		0.89
GERP RS		6.0

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-38285755; COSMIC: COSV59899749; COSMIC: COSV59899749;