rs193920989

Variant names:

• chr14-99660375-G-A
• NM_001127258.3:c.1471G>A

Your query was ambiguous. Multiple possible variants found:

• chr14-99660375-G-A
• chr14-99660375-G-C
• chr14-99660375-G-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001127258.3(HHIPL1):​c.1471G>A​(p.Gly491Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,550 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HHIPL1 NM_001127258.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 10.0

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.983

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HHIPL1	NM_001127258.3	c.1471G>A	p.Gly491Ser	missense_variant	Exon 5 of 9	ENST00000330710.10	NP_001120730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HHIPL1	ENST00000330710.10	c.1471G>A	p.Gly491Ser	missense_variant	Exon 5 of 9	1	NM_001127258.3	ENSP00000330601.5
HHIPL1	ENST00000357223.2	c.1471G>A	p.Gly491Ser	missense_variant	Exon 5 of 8	1		ENSP00000349757.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461550 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727046

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;.
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.071	D
MetaRNN	Pathogenic	0.98	D;D
MetaSVM	Benign	-0.46	T
MutationAssessor	Pathogenic	3.1	M;M
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-5.8	D;D
REVEL	Uncertain	0.64
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		1.0	D;D
Vest4		0.97
MutPred		0.92		Loss of catalytic residue at P487 (P = 0.0814);Loss of catalytic residue at P487 (P = 0.0814);
MVP		0.70
MPC		1.2
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.92
gMVP		0.66

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: chr14-100126712; COSMIC: COSV58091601;