rs1178945140

Variant names:

• chr14-31293911-G-A
• rs1178945140
• NM_015473.4:c.5813C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-31293911-G-A
• chr14-31293911-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015473.4(HEATR5A):​c.5813C>T​(p.Thr1938Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1938N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HEATR5A NM_015473.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.86

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]

ENSG00000257831 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1051999).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HEATR5A	NM_015473.4	c.5813C>T	p.Thr1938Ile	missense_variant	Exon 35 of 36	ENST00000543095.7	NP_056288.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HEATR5A	ENST00000543095.7	c.5813C>T	p.Thr1938Ile	missense_variant	Exon 35 of 36	5	NM_015473.4	ENSP00000437968.2
HEATR5A	ENST00000538864.6	c.4469C>T	p.Thr1490Ile	missense_variant	Exon 27 of 28	5		ENSP00000439979.2
HEATR5A	ENST00000551414.1	n.2006C>T		non_coding_transcript_exon_variant	Exon 2 of 3	2
ENSG00000257831	ENST00000551799.1	n.401-1521G>A		intron_variant	Intron 4 of 5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.91	T
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.081
Sift	Benign	0.10	T
Sift4G	Benign	0.15	T
Vest4		0.17
MutPred		0.45		Loss of disorder (P = 0.0796);
MVP		0.13
ClinPred		0.55	D
GERP RS		4.5
gMVP		0.11

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: rs1178945140; hg19: chr14-31763117;