chr14-99652285-C-A

Variant names:

• chr14-99652285-C-A
• rs368711613
• NM_001127258.3:c.317C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001127258.3(HHIPL1):​c.317C>A​(p.Thr106Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. T106P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HHIPL1 NM_001127258.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.15
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127258.3. 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
	HHIPL1	NM_001127258.3	MANE Select	c.317C>A	p.Thr106Lys	missense	Exon 2 of 9	NP_001120730.1	F1T0G3
	HHIPL1	NM_032425.5		c.317C>A	p.Thr106Lys	missense	Exon 2 of 8	NP_115801.3	Q96JK4-2
	HHIPL1	NM_001329411.2		c.122C>A	p.Thr41Lys	missense	Exon 3 of 9	NP_001316340.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HHIPL1	ENST00000330710.10	TSL:1 MANE Select	c.317C>A	p.Thr106Lys	missense	Exon 2 of 9	ENSP00000330601.5	Q96JK4-1
	HHIPL1	ENST00000357223.2	TSL:1	c.317C>A	p.Thr106Lys	missense	Exon 2 of 8	ENSP00000349757.2	Q96JK4-2
	HHIPL1	ENST00000949017.1		c.317C>A	p.Thr106Lys	missense	Exon 2 of 9	ENSP00000619076.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.19
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		6.2
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.18
Sift	Benign	0.20	T
Sift4G	Benign	0.56	T
Polyphen		0.92	P
Vest4		0.69
MutPred		0.47		Gain of methylation at T106 (P = 0.0199)
MVP		0.51
MPC		1.2
ClinPred		0.97	D
GERP RS		4.8
Varity_R		0.31
gMVP		0.70
Mutation Taster		=37/63	disease causing

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: rs368711613; hg19: chr14-100118622;