chr17-40129280-C-T

Variant names:

• chr17-40129280-C-T
• rs745339351
• NM_001365919.1:c.1028C>T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001365919.1(MSL1):​c.1028C>T​(p.Pro343Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000634 in 1,420,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: MSL1 NM_001365919.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.21

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.229929).
• BS2: High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSL1	NM_001365919.1	c.1028C>T	p.Pro343Leu	missense_variant	Exon 3 of 9	ENST00000398532.9	NP_001352848.1
MSL1	NM_001365920.1	c.1028C>T	p.Pro343Leu	missense_variant	Exon 3 of 8		NP_001352849.1
MSL1	NM_001365921.2	c.1028C>T	p.Pro343Leu	missense_variant	Exon 3 of 3		NP_001352850.1
MSL1	NM_001012241.2	c.239C>T	p.Pro80Leu	missense_variant	Exon 4 of 10		NP_001012241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSL1	ENST00000398532.9	c.1028C>T	p.Pro343Leu	missense_variant	Exon 3 of 9	1	NM_001365919.1	ENSP00000381543.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000330 AC: 7 AN: 211856 Hom.: 0 AF XY: 0.0000345 AC XY: 4 AN XY: 115994

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000300

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000634 AC: 9 AN: 1420198 Hom.: 0 Cov.: 30 AF XY: 0.00000709 AC XY: 5 AN XY: 705674

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000281

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.00000828 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 16, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.239C>T (p.P80L) alteration is located in exon 4 (coding exon 2) of the MSL1 gene. This alteration results from a C to T substitution at nucleotide position 239, causing the proline (P) at amino acid position 80 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	26
DANN	Benign	0.95
DEOGEN2	Benign	0.070	T;T;T;.
Eigen	Uncertain	0.62
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.23	T;T;T;T
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	1.4	L;.;.;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.6	N;.;.;.
REVEL	Benign	0.27
Sift	Uncertain	0.0020	D;.;.;.
Sift4G	Uncertain	0.0080	D;D;D;T
Polyphen		1.0	D;.;.;.
Vest4		0.46
MutPred		0.37		Gain of helix (P = 0.0022);Gain of helix (P = 0.0022);Gain of helix (P = 0.0022);.;
MVP		0.30
MPC		1.6
ClinPred		0.26	T
GERP RS		6.0
Varity_R		0.059
gMVP		0.34

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

LitVar

Other links and lift over

dbSNP: rs745339351; hg19: chr17-38285533;