15-43801787-T-C

Variant names:

• chr15-43801787-T-C
• rs61744182
• NM_016400.4:c.347T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_016400.4(HYPK):​c.347T>C​(p.Leu116Pro) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L116R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HYPK NM_016400.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.79
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.935

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016400.4. 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
	HYPK	NM_016400.4	MANE Select	c.347T>C	p.Leu116Pro	missense	Exon 4 of 4	NP_057484.4
	HYPK	NM_001199885.1		c.*69T>C		3_prime_UTR	Exon 3 of 3	NP_001186814.1	Q9NX55
	SERF2-C15ORF63	NR_037673.1		n.992T>C		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HYPK	ENST00000442995.4	TSL:1 MANE Select	c.347T>C	p.Leu116Pro	missense	Exon 4 of 4	ENSP00000401155.3	Q9NX55-2
	HYPK	ENST00000406925.7	TSL:2	c.347T>C	p.Leu116Pro	missense	Exon 5 of 5	ENSP00000384474.2	Q9NX55-2
	HYPK	ENST00000458412.2	TSL:2	c.*207T>C		3_prime_UTR	Exon 2 of 2	ENSP00000394060.2	J3QT56

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	-0.049	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		7.8
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-6.5	D
REVEL	Pathogenic	0.80
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.99	D
Vest4		0.98
MutPred		0.75		Loss of helix (P = 0.0017)
MVP		0.90
MPC		2.1
ClinPred		1.0	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.98
gMVP		0.97

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: rs61744182; hg19: chr15-44093985;