rs778104807

Variant names:

• chr17-40129265-C-G
• rs778104807
• NM_001365919.1:c.1013C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-40129265-C-G
• chr17-40129265-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001365919.1(MSL1):​c.1013C>G​(p.Thr338Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000213 in 1,406,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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. T338I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MSL1 NM_001365919.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.75
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11184034).

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.1013C>G	p.Thr338Arg	missense	Exon 3 of 9	NP_001352848.1	Q68DK7-1
	MSL1	NM_001365920.1		c.1013C>G	p.Thr338Arg	missense	Exon 3 of 8	NP_001352849.1	J3KSZ8
	MSL1	NM_001365921.2		c.1013C>G	p.Thr338Arg	missense	Exon 3 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.1013C>G	p.Thr338Arg	missense	Exon 3 of 9	ENSP00000381543.3	Q68DK7-1
	MSL1	ENST00000579565.5	TSL:1	c.224C>G	p.Thr75Arg	missense	Exon 4 of 10	ENSP00000462945.1	Q68DK7-3
	MSL1	ENST00000578648.5	TSL:5	c.1013C>G	p.Thr338Arg	missense	Exon 3 of 8	ENSP00000462731.1	J3KSZ8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000213 AC: 3 AN: 1406748 Hom.: 0 Cov.: 30 AF XY: 0.00000286 AC XY: 2 AN XY: 698156

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000329 AC: 1 AN: 30412

American (AMR) AF: 0.00 AC: 0 AN: 29720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22972

East Asian (EAS) AF: 0.00 AC: 0 AN: 38800

South Asian (SAS) AF: 0.00 AC: 0 AN: 77100

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51690

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5480

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1092780

Other (OTH) AF: 0.00 AC: 0 AN: 57794

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000000888178), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Benign	0.87
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.21
Eigen_PC	Benign	0.025
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.7
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.089
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.010	D
Polyphen		0.062	B
Vest4		0.32
MutPred		0.23		Loss of phosphorylation at T338 (P = 0.0011)
MVP		0.093
MPC		0.92
ClinPred		0.52	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.28
gMVP		0.19
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs778104807; hg19: chr17-38285518;