14-99645329-A-T

Variant names:

• chr14-99645329-A-T
• rs776085652
• NM_001127258.3:c.122A>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001127258.3(HHIPL1):​c.122A>T​(p.Gln41Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,459,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: HHIPL1 NM_001127258.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.49
• 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.27527273).

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.122A>T	p.Gln41Leu	missense	Exon 1 of 9	NP_001120730.1	F1T0G3
	HHIPL1	NM_032425.5		c.122A>T	p.Gln41Leu	missense	Exon 1 of 8	NP_115801.3	Q96JK4-2
	HHIPL1	NM_001329411.2		c.61-6895A>T		intron	N/A	NP_001316340.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HHIPL1	ENST00000330710.10	TSL:1 MANE Select	c.122A>T	p.Gln41Leu	missense	Exon 1 of 9	ENSP00000330601.5	Q96JK4-1
	HHIPL1	ENST00000357223.2	TSL:1	c.122A>T	p.Gln41Leu	missense	Exon 1 of 8	ENSP00000349757.2	Q96JK4-2
	HHIPL1	ENST00000949017.1		c.122A>T	p.Gln41Leu	missense	Exon 1 of 9	ENSP00000619076.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152010 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000681 AC: 5 AN: 73372 AF XY: 0.000118

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000191 AC: 25 AN: 1307210 Hom.: 0 Cov.: 31 AF XY: 0.0000295 AC XY: 19 AN XY: 644196

African (AFR) AF: 0.00 AC: 0 AN: 26498

American (AMR) AF: 0.00 AC: 0 AN: 24496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22784

East Asian (EAS) AF: 0.00 AC: 0 AN: 27826

South Asian (SAS) AF: 0.000354 AC: 25 AN: 70610

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34784

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3820

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1042524

Other (OTH) AF: 0.00 AC: 0 AN: 53868

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152120 Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3 AN XY: 74380

African (AFR) AF: 0.00 AC: 0 AN: 41532

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67970

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000129 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Benign	0.77
DEOGEN2	Benign	0.072	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.51	T
M_CAP	Pathogenic	0.58	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.5
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.089
Sift	Benign	0.12	T
Sift4G	Benign	0.51	T
Polyphen		0.087	B
Vest4		0.39
MutPred		0.38		Loss of catalytic residue at Q41 (P = 0.0427)
MVP		0.30
MPC		0.47
ClinPred		0.18	T
GERP RS		1.7
PromoterAI		0.034	Neutral
Varity_R		0.13
gMVP		0.35
Mutation Taster		=89/11	polymorphism

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: rs776085652; hg19: chr14-100111666;