11-94129292-C-G

Variant names:

• chr11-94129292-C-G
• rs77517764
• NM_015368.4:c.-21C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015368.4(PANX1):​c.-21C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0066 in 1,590,262 control chromosomes in the GnomAD database, including 610 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (313 hom., cov: 32)
  • Exomes 𝑓: 0.0036 (297 hom.)
• Consequence: PANX1 NM_015368.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.67
• Publications: 0 publications found

Genes affected

PANX1 (HGNC:8599): (pannexin 1) The protein encoded by this gene belongs to the innexin family. Innexin family members are the structural components of gap junctions. This protein and pannexin 2 are abundantly expressed in central nerve system (CNS) and are coexpressed in various neuronal populations. Studies in Xenopus oocytes suggest that this protein alone and in combination with pannexin 2 may form cell type-specific gap junctions with distinct properties. [provided by RefSeq, Jul 2008]

PANX1 Gene-Disease associations (from GenCC):

• oocyte maturation defect 7

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 11-94129292-C-G is Benign according to our data. Variant chr11-94129292-C-G is described in ClinVar as [Benign]. Clinvar id is 1241308.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PANX1	NM_015368.4	c.-21C>G		5_prime_UTR_variant	Exon 1 of 5	ENST00000227638.8	NP_056183.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PANX1	ENST00000227638.8	c.-21C>G		5_prime_UTR_variant	Exon 1 of 5	1	NM_015368.4	ENSP00000227638.3
PANX1	ENST00000436171.2	c.-21C>G		5_prime_UTR_variant	Exon 1 of 5	1		ENSP00000411461.2

Frequencies

GnomAD3 genomes AF: 0.0346 AC: 5273 AN: 152182 Hom.: 313 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.0215

GnomAD2 exomes AF: 0.00910 AC: 2184 AN: 239908 AF XY: 0.00641

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.00364

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000250

Gnomad OTH exome AF: 0.00398

GnomAD4 exome AF: 0.00362 AC: 5208 AN: 1437962 Hom.: 297 Cov.: 28 AF XY: 0.00304 AC XY: 2161 AN XY: 711442

African (AFR) AF: 0.131 AC: 4297 AN: 32920

American (AMR) AF: 0.00456 AC: 200 AN: 43876

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25624

East Asian (EAS) AF: 0.00 AC: 0 AN: 38770

South Asian (SAS) AF: 0.0000708 AC: 6 AN: 84712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52650

Middle Eastern (MID) AF: 0.00390 AC: 22 AN: 5648

European-Non Finnish (NFE) AF: 0.000212 AC: 232 AN: 1094634

Other (OTH) AF: 0.00763 AC: 451 AN: 59128

GnomAD4 genome AF: 0.0347 AC: 5280 AN: 152300 Hom.: 313 Cov.: 32 AF XY: 0.0333 AC XY: 2481 AN XY: 74480

African (AFR) AF: 0.121 AC: 5047 AN: 41564

American (AMR) AF: 0.0103 AC: 158 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 68030

Other (OTH) AF: 0.0213 AC: 45 AN: 2114

Alfa AF: 0.00303 Hom.: 2

Bravo AF: 0.0395

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 20, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.4
DANN	Benign	0.78
PhyloP100		-2.7
PromoterAI		-0.036	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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: rs77517764; hg19: chr11-93862458;