14-31393927-T-C

Position:

• chr14-31393927-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015473.4(HEATR5A):​c.772+125A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.997 in 670,758 control chromosomes in the GnomAD database, including 333,593 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.99 (74858 hom., cov: 33)
  • Exomes 𝑓: 1.0 (258735 hom.)
• Consequence: HEATR5A NM_015473.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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]

ENSG00000203546 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HEATR5A	NM_015473.4	c.772+125A>G		intron_variant		ENST00000543095.7	NP_056288.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HEATR5A	ENST00000543095.7	c.772+125A>G		intron_variant		5	NM_015473.4	ENSP00000437968.2
ENSG00000203546	ENST00000549185.5	n.*868+125A>G		intron_variant		2		ENSP00000446654.1

Frequencies

GnomAD3 genomes AF: 0.991 AC: 150901 AN: 152226 Hom.: 74802 Cov.: 33

Gnomad AFR AF: 0.969

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.997

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.995

GnomAD4 exome AF: 0.999 AC: 517937 AN: 518414 Hom.: 258735 AF XY: 0.999 AC XY: 269673 AN XY: 269894

Gnomad4 AFR exome AF: 0.970

Gnomad4 AMR exome AF: 0.998

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.998

GnomAD4 genome AF: 0.991 AC: 151017 AN: 152344 Hom.: 74858 Cov.: 33 AF XY: 0.991 AC XY: 73832 AN XY: 74488

Gnomad4 AFR AF: 0.970

Gnomad4 AMR AF: 0.997

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.995

Alfa AF: 0.995 Hom.: 8589

Bravo AF: 0.990

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.49
DANN	Benign	0.20

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

LitVar

Other links and lift over

dbSNP: rs10138277; hg19: chr14-31863133;