14-99652281-C-G

Variant names:

• chr14-99652281-C-G
• NM_001127258.3:c.313C>G

Variant summary

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

The NM_001127258.3(HHIPL1):​c.313C>G​(p.Arg105Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,434 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: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HHIPL1 NM_001127258.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.297

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, 0.814

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HHIPL1	NM_001127258.3	c.313C>G	p.Arg105Gly	missense_variant	Exon 2 of 9	ENST00000330710.10	NP_001120730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HHIPL1	ENST00000330710.10	c.313C>G	p.Arg105Gly	missense_variant	Exon 2 of 9	1	NM_001127258.3	ENSP00000330601.5
HHIPL1	ENST00000357223.2	c.313C>G	p.Arg105Gly	missense_variant	Exon 2 of 8	1		ENSP00000349757.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461434 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727044

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;.
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.34
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.049	D
MetaRNN	Pathogenic	0.81	D;D
MetaSVM	Benign	-0.41	T
MutationAssessor	Pathogenic	3.0	M;M
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-5.7	D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.011	D;D
Polyphen		1.0	D;D
Vest4		0.94
MutPred		0.48		Loss of stability (P = 0.0729);Loss of stability (P = 0.0729);
MVP		0.52
MPC		1.4
ClinPred		1.0	D
GERP RS		0.64
Varity_R		0.76
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: chr14-100118618;