14-93242630-G-T

Position:

• chr14-93242630-G-T

Variant summary

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

The NM_001002860.4(BTBD7):​c.3042C>A​(p.Asp1014Glu) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BTBD7 NM_001002860.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.52

Genes affected

BTBD7 (HGNC:18269): (BTB domain containing 7) Predicted to be involved in regulation of branching involved in salivary gland morphogenesis. Predicted to be located in nucleus. [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=0.034065127).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTBD7	NM_001002860.4	c.3042C>A	p.Asp1014Glu	missense_variant	11/11	ENST00000334746.10	NP_001002860.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTBD7	ENST00000334746.10	c.3042C>A	p.Asp1014Glu	missense_variant	11/11	1	NM_001002860.4	ENSP00000335615.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

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

Mar 16, 2022

The c.3042C>A (p.D1014E) alteration is located in exon 11 (coding exon 10) of the BTBD7 gene. This alteration results from a C to A substitution at nucleotide position 3042, causing the aspartic acid (D) at amino acid position 1014 to be replaced by a glutamic acid (E). 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	0.072
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.0050
DANN	Benign	0.89
DEOGEN2	Benign	0.013	T;.;.
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.048	N
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.034	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.34	N;.;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.37	N;N;N
REVEL	Benign	0.077
Sift	Benign	0.077	T;T;T
Sift4G	Benign	0.51	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.090
MutPred		0.11		Loss of glycosylation at S1012 (P = 0.1491);.;.;
MVP		0.46
MPC		0.16
ClinPred		0.13	T
GERP RS		-12
Varity_R		0.057
gMVP		0.17

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: rs751931563; hg19: chr14-93708976;