rs61744182

Variant names:

• chr15-43801787-T-A
• NM_016400.4:c.347T>A

Your query was ambiguous. Multiple possible variants found:

• chr15-43801787-T-A
• chr15-43801787-T-C
• chr15-43801787-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_016400.4(HYPK):​c.347T>A​(p.Leu116His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HYPK NM_016400.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.79

Genes affected

HYPK (HGNC:18418): (huntingtin interacting protein K) Enables protein N-terminus binding activity. Involved in negative regulation of apoptotic process and protein stabilization. Located in cytoplasm; microtubule cytoskeleton; and nucleoplasm. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

SERF2 (HGNC:10757): (small EDRK-rich factor 2) Involved in protein destabilization. Predicted to be located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SERF2-C15ORF63 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.859

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYPK	NM_016400.4	c.347T>A	p.Leu116His	missense_variant	Exon 4 of 4	ENST00000442995.4	NP_057484.4
HYPK	NM_001199885.1	c.*69T>A		3_prime_UTR_variant	Exon 3 of 3		NP_001186814.1
SERF2-C15ORF63	NR_037673.1	n.992T>A		non_coding_transcript_exon_variant	Exon 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYPK	ENST00000442995.4	c.347T>A	p.Leu116His	missense_variant	Exon 4 of 4	1	NM_016400.4	ENSP00000401155.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	26
DANN	Benign	0.97
DEOGEN2	Uncertain	0.43	T;T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	.;T
M_CAP	Benign	0.082	D
MetaRNN	Pathogenic	0.86	D;D
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.9	M;M
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-6.4	D;D
REVEL	Uncertain	0.59
Sift	Uncertain	0.012	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		0.14	B;B
Vest4		0.94
MutPred		0.67		Loss of stability (P = 0.0088);Loss of stability (P = 0.0088);
MVP		0.84
MPC		1.1
ClinPred		0.99	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.88
gMVP		0.93

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-44093985;