17-40131557-G-T

Variant names:

• chr17-40131557-G-T
• rs772734350
• NM_001365919.1:c.1396G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001365919.1(MSL1):​c.1396G>T​(p.Val466Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,642 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. V466I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: MSL1 NM_001365919.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.56
• 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]

ENSG00000310351 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.20048708).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

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.1396G>T	p.Val466Phe	missense	Exon 4 of 9	NP_001352848.1	Q68DK7-1
	MSL1	NM_001012241.2		c.607G>T	p.Val203Phe	missense	Exon 5 of 10	NP_001012241.1	Q68DK7-3
	MSL1	NM_001365920.1		c.1376-477G>T		intron	N/A	NP_001352849.1	J3KSZ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSL1	ENST00000398532.9	TSL:1 MANE Select	c.1396G>T	p.Val466Phe	missense	Exon 4 of 9	ENSP00000381543.3	Q68DK7-1
	MSL1	ENST00000579565.5	TSL:1	c.607G>T	p.Val203Phe	missense	Exon 5 of 10	ENSP00000462945.1	Q68DK7-3
	MSL1	ENST00000578648.5	TSL:5	c.1376-477G>T		intron	N/A	ENSP00000462731.1	J3KSZ8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461642 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 727114

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

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: 0.00000450 AC: 5 AN: 1111810

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.69	N
PhyloP100		4.6
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.19
Sift	Benign	0.053	T
Sift4G	Benign	0.12	T
Vest4		0.38
MutPred		0.20		Gain of sheet (P = 0.0827)
MVP		0.29
MPC		0.89
ClinPred		0.42	T
GERP RS		6.0
Varity_R		0.11
gMVP		0.44

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: rs772734350; hg19: chr17-38287810;