chr7-97006070-G-C

Variant names:

• chr7-97006070-G-C
• NM_005222.4:c.93G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005222.4(DLX6):​c.93G>C​(p.Gln31His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 1,419,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: DLX6 NM_005222.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.433

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.389844).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLX6	NM_005222.4	c.93G>C	p.Gln31His	missense_variant	Exon 1 of 3	ENST00000518156.3	NP_005213.3
DLX6-AS1	NR_015448.1	n.141+7855C>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLX6	ENST00000518156.3	c.93G>C	p.Gln31His	missense_variant	Exon 1 of 3	1	NM_005222.4	ENSP00000428480.2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000211 AC: 3 AN: 1419484 Hom.: 0 Cov.: 34 AF XY: 0.00000142 AC XY: 1 AN XY: 702700

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000275

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	3.5
DANN	Benign	0.95
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.43	T
M_CAP	Pathogenic	0.92	D
MetaRNN	Benign	0.39	T
MetaSVM	Uncertain	0.17	D
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.41	N
REVEL	Uncertain	0.39
Sift	Benign	0.48	T
Sift4G	Benign	0.21	T
Vest4		0.36
MutPred		0.31		Gain of MoRF binding (P = 0.2946);
MVP		0.80
MPC		0.67
ClinPred		0.14	T
GERP RS		-0.89
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-96635382; COSMIC: COSV104528183; COSMIC: COSV104528183;