17-40126319-T-G

Variant names:

• chr17-40126319-T-G
• rs773739124
• NM_001365919.1:c.905T>G

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L302P) has been classified as Uncertain significance.

• 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365919.1. 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
	MSL1	NM_001365919.1	MANE Select	c.905T>G	p.Leu302Arg	missense	Exon 2 of 9	NP_001352848.1	Q68DK7-1
	MSL1	NM_001365920.1		c.905T>G	p.Leu302Arg	missense	Exon 2 of 8	NP_001352849.1	J3KSZ8
	MSL1	NM_001365921.2		c.905T>G	p.Leu302Arg	missense	Exon 2 of 3	NP_001352850.1	J3QQY0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSL1	ENST00000398532.9	TSL:1 MANE Select	c.905T>G	p.Leu302Arg	missense	Exon 2 of 9	ENSP00000381543.3	Q68DK7-1
	MSL1	ENST00000579565.5	TSL:1	c.116T>G	p.Leu39Arg	missense	Exon 3 of 10	ENSP00000462945.1	Q68DK7-3
	MSL1	ENST00000578648.5	TSL:5	c.905T>G	p.Leu302Arg	missense	Exon 2 of 8	ENSP00000462731.1	J3KSZ8

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

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111870

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.69	N
PhyloP100		3.2
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.18	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.043	D
Polyphen		0.99	D
Vest4		0.32
MutPred		0.24		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
Mutation Taster		=61/39	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: rs773739124; hg19: chr17-38282572;