NM_016400.4:c.44C>A

Variant names:

• chr15-43800666-C-A
• rs142096250
• NM_016400.4:c.44C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016400.4(HYPK):​c.44C>A​(p.Thr15Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,840 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: HYPK NM_016400.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.75

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11776063).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HYPK	NM_016400.4	c.44C>A	p.Thr15Asn	missense_variant	Exon 1 of 4	ENST00000442995.4	NP_057484.4
HYPK	NM_001199885.1	c.68C>A	p.Thr23Asn	missense_variant	Exon 1 of 3		NP_001186814.1
SERF2-C15ORF63	NR_037673.1	n.689C>A		non_coding_transcript_exon_variant	Exon 3 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HYPK	ENST00000442995.4	c.44C>A	p.Thr15Asn	missense_variant	Exon 1 of 4	1	NM_016400.4	ENSP00000401155.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461840 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727224

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

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.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.0039	T;T;T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.069
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.83	.;T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.69	N;N;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	0.22	N;N;N
REVEL	Benign	0.029
Sift	Benign	0.50	T;T;T
Sift4G	Benign	0.52	T;T;T
Polyphen		0.0020	B;B;.
Vest4		0.25
MutPred		0.15		Loss of phosphorylation at T23 (P = 0.0131);Loss of phosphorylation at T23 (P = 0.0131);Loss of phosphorylation at T23 (P = 0.0131);
MVP		0.61
MPC		0.78
ClinPred		0.37	T
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.47

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: rs142096250; hg19: chr15-44092864;