14-99645268-C-T

Variant names:

• chr14-99645268-C-T
• rs1053152358
• NM_001127258.3:c.61C>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001127258.3(HHIPL1):​c.61C>T​(p.Pro21Ser) variant causes a missense change. 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: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HHIPL1 NM_001127258.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.54

Genes affected

HHIPL1 (HGNC:19710): (HHIP like 1) This gene encodes a protein that belongs to the glucose/sorbosone dehydrogenase family. The encoded protein also contains a domain that binds folate and reduced folic acid derivatives. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.801

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HHIPL1	NM_001127258.3	c.61C>T	p.Pro21Ser	missense_variant	Exon 1 of 9	ENST00000330710.10	NP_001120730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HHIPL1	ENST00000330710.10	c.61C>T	p.Pro21Ser	missense_variant	Exon 1 of 9	1	NM_001127258.3	ENSP00000330601.5
HHIPL1	ENST00000357223.2	c.61C>T	p.Pro21Ser	missense_variant	Exon 1 of 8	1		ENSP00000349757.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1266968 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 622048

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

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.: 34

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	0.0063	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;.
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Pathogenic	0.47	D
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Benign	-0.31	T
MutationAssessor	Pathogenic	3.0	M;M
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-6.1	D;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.016	D;D
Polyphen		1.0	D;D
Vest4		0.74
MutPred		0.62		Gain of helix (P = 0.062);Gain of helix (P = 0.062);
MVP		0.53
MPC		1.2
ClinPred		1.0	D
GERP RS		3.7
Varity_R		0.46
gMVP		0.61

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: rs1053152358; hg19: chr14-100111605;