Variant chr8-132071382-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001145095.3(HHLA1):c.1427G>A(p.Cys476Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000643 in 1,399,336 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

HHLA1
NM_001145095.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.61

Variant links:

Genes affected

HHLA1 (HGNC:4904): (HHLA1 neighbor of OC90) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

HHLA1 links:

ENSG00000258417 (HGNC:):

ENSG00000258417 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HHLA1	NM_001145095.3 linkuse as main transcript	c.1427G>A	p.Cys476Tyr	missense_variant	15/17	ENST00000414222.2	NP_001138567.1	C9JL84-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HHLA1	ENST00000414222.2 linkuse as main transcript	c.1427G>A	p.Cys476Tyr	missense_variant	15/17	5	NM_001145095.3	ENSP00000388322.1	C9JL84-1
ENSG00000258417	ENST00000262283.5 linkuse as main transcript	c.541+4673G>A		intron_variant		5		ENSP00000262283.5	I6L893
HHLA1	ENST00000473291.1 linkuse as main transcript	n.1889G>A		non_coding_transcript_exon_variant	5/7	1
HHLA1	ENST00000673615.1 linkuse as main transcript	c.1535G>A	p.Cys512Tyr	missense_variant	16/18			ENSP00000500443.1	A0A5F9ZHM0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000192

AC:

AN:

156156

Hom.:

AF XY:

0.0000242

AC XY:

AN XY:

82740

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000810

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000166

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000643

AC:

AN:

1399336

Hom.:

Cov.:

AF XY:

0.00000724

AC XY:

AN XY:

690178

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

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:

0.00000463

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000398

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 18, 2023

The c.1427G>A (p.C476Y) alteration is located in exon 14 (coding exon 14) of the HHLA1 gene. This alteration results from a G to A substitution at nucleotide position 1427, causing the cysteine (C) at amino acid position 476 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Pathogenic

0.35

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;.

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.030

MetaRNN

Uncertain

0.70

D;D

MetaSVM

Benign

-0.34

MutationAssessor

Uncertain

2.1

M;.

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.5

D;D

REVEL

Uncertain

0.33

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.87

MVP

0.26

ClinPred

0.90

GERP RS

5.9

Varity_R

0.70

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over