Variant chr4-127805739-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014278.4(HSPA4L):c.1190T>G(p.Leu397Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,460,678 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: 0.0000034 ( 0 hom. )

Consequence

HSPA4L
NM_014278.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.64

Variant links:

Genes affected

HSPA4L (HGNC:17041): (heat shock protein family A (Hsp70) member 4 like) The protein encoded by this gene is heat shock inducible and may act as a chaperone. The encoded protein can protect the heat-shocked cell against the harmful effects of aggregated proteins. This gene is highly expressed in leukemia cells and may be a good target for therapeutic intervention. Several transcripts encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

HSPA4L 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
HSPA4L	NM_014278.4 linkuse as main transcript	c.1190T>G	p.Leu397Arg	missense_variant	10/19	ENST00000296464.9	NP_055093.2	O95757A0A140VKE7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HSPA4L	ENST00000296464.9 linkuse as main transcript	c.1190T>G	p.Leu397Arg	missense_variant	10/19	1	NM_014278.4	ENSP00000296464.3	O95757
HSPA4L	ENST00000508549.5 linkuse as main transcript	c.1067T>G	p.Leu356Arg	missense_variant	9/13	1		ENSP00000427305.1	D6RJ96
HSPA4L	ENST00000508776.5 linkuse as main transcript	c.1190T>G	p.Leu397Arg	missense_variant	11/20	2		ENSP00000422482.1	O95757
HSPA4L	ENST00000505726.1 linkuse as main transcript	c.1112T>G	p.Leu371Arg	missense_variant	10/19	2		ENSP00000425645.1	E9PDE8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251086

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1460678

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726664

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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

Apr 01, 2024

The c.1190T>G (p.L397R) alteration is located in exon 10 (coding exon 10) of the HSPA4L gene. This alteration results from a T to G substitution at nucleotide position 1190, causing the leucine (L) at amino acid position 397 to be replaced by an arginine (R). 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

0.32

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

T;T;T;T

Eigen

Benign

0.081

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.94

.;D;D;D

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.55

D;D;D;D

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.22

N;N;.;.

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.1

D;D;D;D

REVEL

Benign

0.18

Sift

Uncertain

0.0040

D;D;D;D

Sift4G

Benign

0.24

T;T;T;T

Polyphen

0.29

B;B;.;P

Vest4

0.68

MutPred

0.81

Gain of methylation at L397 (P = 0.0266);Gain of methylation at L397 (P = 0.0266);.;.;

MVP

0.53

MPC

0.29

ClinPred

0.38

GERP RS

4.5

Varity_R

0.59

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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