7-149720047-C-G

Position:

• chr7-149720047-C-G

Variant summary

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

The ENST00000496259.6(KRBA1):​c.179C>G​(p.Pro60Arg) 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. 12/20 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: KRBA1 ENST00000496259.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.39

Genes affected

KRBA1 (HGNC:22228): (KRAB-A domain containing 1) Predicted to be involved in regulation of transcription, DNA-templated. [provided by Alliance of Genome Resources, Apr 2022]

KRBA1 (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=0.17600593).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRBA1	NM_001290187.2	c.179C>G	p.Pro60Arg	missense_variant	3/17	ENST00000496259.6	NP_001277116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRBA1	ENST00000496259.6	c.179C>G	p.Pro60Arg	missense_variant	3/17	1	NM_001290187.2	ENSP00000418647.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Dec 20, 2023

The c.74C>G (p.P25R) alteration is located in exon 3 (coding exon 2) of the KRBA1 gene. This alteration results from a C to G substitution at nucleotide position 74, causing the proline (P) at amino acid position 25 to be replaced by an arginine (R). 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	0.22
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Benign	0.92
DEOGEN2	Benign	0.18	.;T;T;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.58	T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	.;M;.;M
MutationTaster	Benign	0.64	N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-5.7	D;D;D;D
REVEL	Benign	0.092
Sift	Benign	0.054	T;D;T;D
Sift4G	Benign	0.45	T;T;T;T
Polyphen		0.39	.;B;.;.
Vest4		0.43
MutPred		0.48		.;Loss of glycosylation at P25 (P = 0.0243);Loss of glycosylation at P25 (P = 0.0243);Loss of glycosylation at P25 (P = 0.0243);
MVP		0.23
ClinPred		0.53	D
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.051
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: chr7-149417138;