chr17-40126319-T-G

Variant names:

• chr17-40126319-T-G
• NM_001365919.1:c.905T>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001365919.1(MSL1):​c.905T>G​(p.Leu302Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,710 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MSL1 NM_001365919.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.17

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3024507).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSL1	NM_001365919.1	c.905T>G	p.Leu302Arg	missense_variant	Exon 2 of 9	ENST00000398532.9	NP_001352848.1
MSL1	NM_001365920.1	c.905T>G	p.Leu302Arg	missense_variant	Exon 2 of 8		NP_001352849.1
MSL1	NM_001365921.2	c.905T>G	p.Leu302Arg	missense_variant	Exon 2 of 3		NP_001352850.1
MSL1	NM_001012241.2	c.116T>G	p.Leu39Arg	missense_variant	Exon 3 of 10		NP_001012241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSL1	ENST00000398532.9	c.905T>G	p.Leu302Arg	missense_variant	Exon 2 of 9	1	NM_001365919.1	ENSP00000381543.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461710 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727136

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.049	T;T;T;.;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.81	T;T;T;T;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.30	T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.69	N;.;.;.;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.18	N;.;.;.;.
REVEL	Uncertain	0.32
Sift	Uncertain	0.0080	D;.;.;.;.
Sift4G	Uncertain	0.043	D;T;T;T;D
Polyphen		0.99	D;.;.;.;.
Vest4		0.32
MutPred		0.24		Gain of solvent accessibility (P = 0.0086);Gain of solvent accessibility (P = 0.0086);Gain of solvent accessibility (P = 0.0086);.;.;
MVP		0.18
MPC		1.7
ClinPred		0.64	D
GERP RS		5.8
Varity_R		0.24
gMVP		0.36

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: chr17-38282572;