15-79293297-G-C

Position:

• chr15-79293297-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001146341.2(ANKRD34C):​c.13G>C​(p.Asp5His) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKRD34C NM_001146341.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.587

Genes affected

ANKRD34C (HGNC:33888): (ankyrin repeat domain 34C)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055750906).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD34C	NM_001146341.2	c.13G>C	p.Asp5His	missense_variant	2/2	ENST00000421388.4	NP_001139813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD34C	ENST00000421388.4	c.13G>C	p.Asp5His	missense_variant	2/2	6	NM_001146341.2	ENSP00000401089.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Sep 14, 2022

The c.13G>C (p.D5H) alteration is located in exon 2 (coding exon 1) of the ANKRD34C gene. This alteration results from a G to C substitution at nucleotide position 13, causing the aspartic acid (D) at amino acid position 5 to be replaced by a histidine (H). 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	0.20
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	12
DANN	Benign	0.91
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.028
Sift	Benign	0.099	T
Sift4G	Benign	0.17	T
Polyphen		0.26	B
Vest4		0.19
MutPred		0.46		Loss of solvent accessibility (P = 0.1279);
MVP		0.040
ClinPred		0.16	T
GERP RS		1.4
Varity_R		0.091
gMVP		0.35

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: rs183612932; hg19: chr15-79585639;