chr7-97006061-G-T

Variant names:

• chr7-97006061-G-T
• rs758574464
• NM_005222.4:c.84G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005222.4(DLX6):​c.84G>T​(p.Gln28His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,426,684 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 29)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DLX6 NM_005222.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0480
• Publications: 0 publications found

Genes affected

DLX6 (HGNC:2919): (distal-less homeobox 6) This gene encodes a member of a homeobox transcription factor gene family similiar to the Drosophila distal-less gene. This family is comprised of at least 6 different members that encode proteins with roles in forebrain and craniofacial development. This gene is in a tail-to-tail configuration with another member of the family on the long arm of chromosome 7. [provided by RefSeq, Jul 2008]

DLX6-AS1 (HGNC:37151): (DLX6 antisense RNA 1) Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26814094).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005222.4. 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
	DLX6	NM_005222.4	MANE Select	c.84G>T	p.Gln28His	missense	Exon 1 of 3	NP_005213.3
	DLX6-AS1	NR_015448.1		n.141+7864C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLX6	ENST00000518156.3	TSL:1 MANE Select	c.84G>T	p.Gln28His	missense	Exon 1 of 3	ENSP00000428480.2	P56179-3
	DLX6-AS1	ENST00000458352.5	TSL:1	n.615+5764C>A		intron	N/A
	DLX6-AS1	ENST00000430027.3	TSL:2	n.141+7864C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD2 exomes AF: 0.0000106 AC: 2 AN: 188532 AF XY: 0.00000975

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000731

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1426684 Hom.: 0 Cov.: 34 AF XY: 0.00000141 AC XY: 1 AN XY: 706858

African (AFR) AF: 0.00 AC: 0 AN: 32628

American (AMR) AF: 0.00 AC: 0 AN: 39904

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25608

East Asian (EAS) AF: 0.0000265 AC: 1 AN: 37702

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81624

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1095150

Other (OTH) AF: 0.00 AC: 0 AN: 59086

GnomAD4 genome Cov.: 29

ExAC AF: 0.00000866 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	17
DANN	Benign	0.93
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.46	T
M_CAP	Pathogenic	0.94	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.56	T
PhyloP100		-0.048
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.37	N
REVEL	Uncertain	0.30
Sift	Benign	0.52	T
Sift4G	Benign	0.63	T
Vest4		0.36
MutPred		0.30		Gain of catalytic residue at Q28 (P = 0.1444)
MVP		0.63
MPC		1.2
ClinPred		0.044	T
GERP RS		-0.022
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.32
Mutation Taster		=89/11	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: rs758574464; hg19: chr7-96635373;