3-42942065-T-C

Variant names:

• chr3-42942065-T-C
• NM_001205272.2:c.271T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001205272.2(KRABD1):​c.271T>C​(p.Trp91Arg) 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. 16/22 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KRABD1 NM_001205272.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.923
• Publications: 0 publications found

Genes affected

KRABD1 (HGNC:38708): (KRAB box domain containing 1) Predicted to be involved in regulation of transcription, DNA-templated. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000290317 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09555125).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001205272.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRABD1	NM_001205272.2	MANE Select	c.271T>C	p.Trp91Arg	missense	Exon 4 of 5	NP_001192201.1	C9JBD0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRBOX1	ENST00000383748.9	TSL:1 MANE Select	c.271T>C	p.Trp91Arg	missense	Exon 4 of 5	ENSP00000373254.5	C9JBD0-1
	KRBOX1	ENST00000418176.1	TSL:1	c.271T>C	p.Trp91Arg	missense	Exon 3 of 4	ENSP00000388094.1	C9JBD0-1
	ENSG00000290317	ENST00000426937.5	TSL:3	c.271T>C	p.Trp91Arg	missense	Exon 6 of 7	ENSP00000413859.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1382256 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 682154

African (AFR) AF: 0.00 AC: 0 AN: 31552

American (AMR) AF: 0.00 AC: 0 AN: 35694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25172

East Asian (EAS) AF: 0.00 AC: 0 AN: 35722

South Asian (SAS) AF: 0.00 AC: 0 AN: 79206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5672

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1077448

Other (OTH) AF: 0.00 AC: 0 AN: 57892

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.034
DANN	Benign	0.30
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00043	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.92
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.040
Sift	Benign	0.078	T
Sift4G	Benign	0.094	T
Polyphen		0.0	B
Vest4		0.084
MutPred		0.55		Gain of solvent accessibility (P = 0.0374)
MVP		0.13
MPC		0.14
ClinPred		0.076	T
GERP RS		-6.0
Varity_R		0.063
gMVP		0.042
Mutation Taster		=97/3	polymorphism

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

hg19: chr3-42983557;