chr14-31293496-G-C

Position:

• chr14-31293496-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015473.4(HEATR5A):​c.5950C>G​(p.Leu1984Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,610 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: HEATR5A NM_015473.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.41

Genes affected

HEATR5A (HGNC:20276): (HEAT repeat containing 5A) Predicted to be involved in endocytosis; protein localization; and retrograde transport, endosome to Golgi. Predicted to be located in cytosol. Predicted to be active in endocytic vesicle. [provided by Alliance of Genome Resources, Apr 2022]

HEATR5A (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32527855).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEATR5A	NM_015473.4	c.5950C>G	p.Leu1984Val	missense_variant	36/36	ENST00000543095.7	NP_056288.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HEATR5A	ENST00000543095.7	c.5950C>G	p.Leu1984Val	missense_variant	36/36	5	NM_015473.4	ENSP00000437968.2
HEATR5A	ENST00000538864.6	c.4606C>G	p.Leu1536Val	missense_variant	28/28	5		ENSP00000439979.2
HEATR5A	ENST00000551414.1	n.2143C>G		non_coding_transcript_exon_variant	3/3	2
ENSG00000257831	ENST00000551799.1	n.401-1936G>C		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461610 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727094

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

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.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 08, 2024

The c.5950C>G (p.L1984V) alteration is located in exon 36 (coding exon 35) of the HEATR5A gene. This alteration results from a C to G substitution at nucleotide position 5950, causing the leucine (L) at amino acid position 1984 to be replaced by a valine (V). 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
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.093	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.33	T
MetaSVM	Uncertain	0.38	D
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.7	D
REVEL	Pathogenic	0.68
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.21
MutPred		0.68		Loss of stability (P = 0.1767);
MVP		0.48
ClinPred		1.0	D
GERP RS		5.6
gMVP		0.55

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-31762702;