14-93242393-G-T

Position:

• chr14-93242393-G-T

Variant summary

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

The NM_001002860.4(BTBD7):​c.3279C>A​(p.Asp1093Glu) 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. 14/21 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: 0.255

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 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=0.09511337).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTBD7	NM_001002860.4	c.3279C>A	p.Asp1093Glu	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.3279C>A	p.Asp1093Glu	missense_variant	11/11	1	NM_001002860.4	ENSP00000335615.5

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

Jun 30, 2022

The c.3279C>A (p.D1093E) 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 3279, causing the aspartic acid (D) at amino acid position 1093 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	0.095
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T;.;.
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.74	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.095	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;.;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.43	N;N;N
REVEL	Benign	0.042
Sift	Uncertain	0.025	D;D;D
Sift4G	Benign	0.11	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.032
MutPred		0.20		Loss of loop (P = 0.0235);.;.;
MVP		0.45
MPC		0.16
ClinPred		0.17	T
GERP RS		3.1
Varity_R		0.036
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr14-93708739;