1-18481511-A-G

Position:

• chr1-18481511-A-G

Variant summary

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

The NM_152375.3(KLHDC7A):​c.530A>G​(p.Asp177Gly) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KLHDC7A NM_152375.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.366

Genes affected

KLHDC7A (HGNC:26791): (kelch domain containing 7A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.05403909).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHDC7A	NM_152375.3	c.530A>G	p.Asp177Gly	missense_variant	1/1	ENST00000400664.3	NP_689588.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHDC7A	ENST00000400664.3	c.530A>G	p.Asp177Gly	missense_variant	1/1	6	NM_152375.3	ENSP00000383505.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 68

GnomAD4 genome Cov.: 33

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

Jan 08, 2024

The c.530A>G (p.D177G) alteration is located in exon 1 (coding exon 1) of the KLHDC7A gene. This alteration results from a A to G substitution at nucleotide position 530, causing the aspartic acid (D) at amino acid position 177 to be replaced by a glycine (G). 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	0.068
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	5.0
DANN	Benign	0.60
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.058
Sift	Benign	0.33	T
Sift4G	Benign	0.50	T
Polyphen		0.0	B
Vest4		0.061
MutPred		0.17		Loss of solvent accessibility (P = 0.0151);
MVP		0.22
MPC		0.49
ClinPred		0.97	D
GERP RS		0.76
Varity_R		0.046
gMVP		0.15

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: chr1-18808005;