NM_001387567.1:c.179C>G

Variant names:

• chr14-105248890-C-G
• rs1165699455
• NM_001387567.1:c.179C>G

Variant summary

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

The NM_001387567.1(BTBD6):​c.179C>G​(p.Ala60Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000486 in 987,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000069 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000045 (0 hom.)
• Consequence: BTBD6 NM_001387567.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.27
• Publications: 0 publications found

Genes affected

BTBD6 (HGNC:19897): (BTB domain containing 6) Predicted to be involved in neurogenesis. Predicted to be located in cytoplasm. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

BRF1 (HGNC:11551): (BRF1 RNA polymerase III transcription initiation factor subunit) This gene encodes one of the three subunits of the RNA polymerase III transcription factor complex. This complex plays a central role in transcription initiation by RNA polymerase III on genes encoding tRNA, 5S rRNA, and other small structural RNAs. The gene product belongs to the TF2B family. Several alternatively spliced variants encoding different isoforms, that function at different promoters transcribed by RNA polymerase III, have been identified. [provided by RefSeq, Jun 2011]

BRF1 Gene-Disease associations (from GenCC):

• cerebellar-facial-dental syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• colorectal adenoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

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=0.111497074).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387567.1. 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
	BTBD6	NM_001387567.1	MANE Select	c.179C>G	p.Ala60Gly	missense	Exon 1 of 4	NP_001374496.1	A0A8C8KHP4
	BRF1	NM_001519.4	MANE Select	c.544+3617G>C		intron	N/A	NP_001510.2
	BTBD6	NM_033271.3		c.20C>G	p.Ala7Gly	missense	Exon 2 of 5	NP_150374.2	Q96KE9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTBD6	ENST00000392554.8	TSL:1 MANE Select	c.179C>G	p.Ala60Gly	missense	Exon 1 of 4	ENSP00000376337.4	Q96KE9-3
	BRF1	ENST00000547530.7	TSL:1 MANE Select	c.544+3617G>C		intron	N/A	ENSP00000448387.2	Q92994-1
	BRF1	ENST00000379937.6	TSL:1	c.463+3617G>C		intron	N/A	ENSP00000369269.2	Q92994-5

Frequencies

GnomAD3 genomes AF: 0.0000685 AC: 10 AN: 145962 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000493

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00236

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000451 AC: 38 AN: 842008 Hom.: 0 Cov.: 30 AF XY: 0.0000385 AC XY: 15 AN XY: 389572

African (AFR) AF: 0.00 AC: 0 AN: 15932

American (AMR) AF: 0.00 AC: 0 AN: 1230

Ashkenazi Jewish (ASJ) AF: 0.00353 AC: 19 AN: 5384

East Asian (EAS) AF: 0.00 AC: 0 AN: 3986

South Asian (SAS) AF: 0.00 AC: 0 AN: 17298

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1660

European-Non Finnish (NFE) AF: 0.0000130 AC: 10 AN: 767538

Other (OTH) AF: 0.000324 AC: 9 AN: 27802

GnomAD4 genome AF: 0.0000685 AC: 10 AN: 145962 Hom.: 0 Cov.: 32 AF XY: 0.0000563 AC XY: 4 AN XY: 70990

African (AFR) AF: 0.0000493 AC: 2 AN: 40568

American (AMR) AF: 0.00 AC: 0 AN: 14758

Ashkenazi Jewish (ASJ) AF: 0.00236 AC: 8 AN: 3384

East Asian (EAS) AF: 0.00 AC: 0 AN: 5038

South Asian (SAS) AF: 0.00 AC: 0 AN: 4788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65728

Other (OTH) AF: 0.00 AC: 0 AN: 2026

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000128

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	0.089
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.31	T
M_CAP	Pathogenic	0.38	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.3
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.17
Sift	Benign	0.047	D
Sift4G	Benign	0.38	T
Polyphen		0.0030	B
Vest4		0.18
MutPred		0.12		Gain of catalytic residue at A7 (P = 0.0207)
MVP		0.56
MPC		0.39
ClinPred		0.13	T
GERP RS		1.5
PromoterAI		-0.093	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.066
gMVP		0.49
Mutation Taster		=96/4	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

dbSNP: rs1165699455; hg19: chr14-105715227;