Variant 8-132076100-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001145095.3(HHLA1):c.1270G>T(p.Ala424Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

HHLA1
NM_001145095.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.42

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06335673).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HHLA1	NM_001145095.3 linkuse as main transcript	c.1270G>T	p.Ala424Ser	missense_variant	14/17	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.1270G>T	p.Ala424Ser	missense_variant	14/17	5	NM_001145095.3	ENSP00000388322.1	C9JL84-1
ENSG00000258417	ENST00000262283.5 linkuse as main transcript	c.496G>T	p.Ala166Ser	missense_variant	4/18	5		ENSP00000262283.5	I6L893
HHLA1	ENST00000473291.1 linkuse as main transcript	n.1732G>T		non_coding_transcript_exon_variant	4/7	1
HHLA1	ENST00000673615.1 linkuse as main transcript	c.1378G>T	p.Ala460Ser	missense_variant	15/18			ENSP00000500443.1	A0A5F9ZHM0

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000128

AC:

AN:

155722

Hom.:

AF XY:

0.0000242

AC XY:

AN XY:

82558

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000184

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

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

Mar 05, 2024

The c.1270G>T (p.A424S) alteration is located in exon 13 (coding exon 13) of the HHLA1 gene. This alteration results from a G to T substitution at nucleotide position 1270, causing the alanine (A) at amino acid position 424 to be replaced by a serine (S). 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

Benign

0.076

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.71

CADD

Benign

8.9

DANN

Benign

0.91

DEOGEN2

Benign

0.0013

.;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.34

T;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.063

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

.;N;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.12

N;N;N

REVEL

Benign

0.047

Sift

Benign

0.082

T;T;T

Sift4G

Benign

0.28

T;T;T

Polyphen

0.0070

.;B;.

Vest4

0.18

MutPred

0.15

.;Gain of glycosylation at A424 (P = 0.0044);.;

MVP

0.067

ClinPred

0.035

GERP RS

3.2

Varity_R

0.034

gMVP

0.090

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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