rs754002170

Variant names:

• chr6-116252831-C-A
• rs754002170
• NM_021648.5:c.1178G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-116252831-C-A
• chr6-116252831-C-T

Variant summary

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

The NM_021648.5(TSPYL4):​c.1178G>T​(p.Arg393Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000692 in 1,446,070 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R393K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TSPYL4 NM_021648.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.41
• Publications: 0 publications found

Genes affected

TSPYL4 (HGNC:21559): (TSPY like 4) Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in nucleosome assembly. Predicted to be active in chromatin and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSPYL4	NM_021648.5	c.1178G>T	p.Arg393Ile	missense_variant	Exon 1 of 1	ENST00000420283.3	NP_067680.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSPYL4	ENST00000420283.3	c.1178G>T	p.Arg393Ile	missense_variant	Exon 1 of 1	6	NM_021648.5	ENSP00000410943.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1446070 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 717754

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

African (AFR) AF: 0.00 AC: 0 AN: 33186

American (AMR) AF: 0.00 AC: 0 AN: 42246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25786

East Asian (EAS) AF: 0.00 AC: 0 AN: 39184

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 83900

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103788

Other (OTH) AF: 0.00 AC: 0 AN: 59860

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0095	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.4
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.13
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.35
MutPred		0.39		Loss of MoRF binding (P = 0.0189);
MVP		0.76
MPC		1.4
ClinPred		0.99	D
GERP RS		3.7
Varity_R		0.45
gMVP		0.44
Mutation Taster		=93/7	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: rs754002170; hg19: chr6-116573994;