14-31393927-T-C

Variant names:

• chr14-31393927-T-C
• rs10138277
• NM_015473.4:c.772+125A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HEATR5A	NM_015473.4	c.772+125A>G		intron_variant	Intron 6 of 35	ENST00000543095.7	NP_056288.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEATR5A	ENST00000543095.7	c.772+125A>G		intron_variant	Intron 6 of 35	5	NM_015473.4	ENSP00000437968.2
ENSG00000203546	ENST00000549185.5	n.*868+125A>G		intron_variant	Intron 8 of 24	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

African (AFR) AF: 0.970 AC: 12137 AN: 12518

American (AMR) AF: 0.998 AC: 14661 AN: 14688

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 13562 AN: 13562

East Asian (EAS) AF: 1.00 AC: 27962 AN: 27962

South Asian (SAS) AF: 1.00 AC: 41807 AN: 41808

European-Finnish (FIN) AF: 1.00 AC: 26737 AN: 26738

Middle Eastern (MID) AF: 1.00 AC: 2115 AN: 2116

European-Non Finnish (NFE) AF: 1.00 AC: 351424 AN: 351438

Other (OTH) AF: 0.998 AC: 27532 AN: 27584

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

African (AFR) AF: 0.970 AC: 40311 AN: 41578

American (AMR) AF: 0.997 AC: 15259 AN: 15304

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5174 AN: 5174

South Asian (SAS) AF: 1.00 AC: 4825 AN: 4826

European-Finnish (FIN) AF: 1.00 AC: 10628 AN: 10628

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68036 AN: 68040

Other (OTH) AF: 0.995 AC: 2106 AN: 2116

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
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10138277; hg19: chr14-31863133;