chr6-105100975-C-T

Variant names:

• chr6-105100975-C-T
• rs221657
• NM_001199563.2:c.*114G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001199563.2(POPDC1):​c.*114G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.956 in 1,265,296 control chromosomes in the GnomAD database, including 578,230 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.96 (70836 hom., cov: 31)
  • Exomes 𝑓: 0.95 (507394 hom.)
• Consequence: POPDC1 NM_001199563.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.134
• Publications: 5 publications found

Genes affected

POPDC1 (HGNC:1152): (blood vessel epicardial substance) This gene encodes a member of the POP family of proteins containing three putative transmembrane domains. This gene is expressed in cardiac and skeletal muscle and may play an important role in development of these tissues. The mouse ortholog may be involved in the regeneration of adult skeletal muscle and may act as a cell adhesion molecule in coronary vasculogenesis. Three transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Dec 2010]

POPDC1 Gene-Disease associations (from GenCC):

• autosomal recessive limb-girdle muscular dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive limb-girdle muscular dystrophy type 2X

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• tetralogy of fallot

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 6-105100975-C-T is Benign according to our data. Variant chr6-105100975-C-T is described in ClinVar as Benign. ClinVar VariationId is 1192585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.984 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199563.2. 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
	POPDC1	NM_001199563.2	MANE Select	c.*114G>A		3_prime_UTR	Exon 8 of 8	NP_001186492.1	Q8NE79
	POPDC1	NM_007073.4		c.*114G>A		3_prime_UTR	Exon 8 of 8	NP_009004.2	Q8NE79
	POPDC1	NM_147147.4		c.*114G>A		3_prime_UTR	Exon 8 of 8	NP_671488.1	Q8NE79

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POPDC1	ENST00000314641.10	TSL:1 MANE Select	c.*114G>A		3_prime_UTR	Exon 8 of 8	ENSP00000313172.5	Q8NE79
	POPDC1	ENST00000336775.9	TSL:1	c.*114G>A		3_prime_UTR	Exon 8 of 8	ENSP00000337259.5	Q8NE79
	POPDC1	ENST00000446408.2	TSL:1	c.*114G>A		3_prime_UTR	Exon 8 of 8	ENSP00000397310.2	Q8NE79

Frequencies

GnomAD3 genomes AF: 0.964 AC: 146730 AN: 152136 Hom.: 70775 Cov.: 31

Gnomad AFR AF: 0.992

Gnomad AMI AF: 0.974

Gnomad AMR AF: 0.966

Gnomad ASJ AF: 0.934

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.926

Gnomad FIN AF: 0.952

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.957

Gnomad OTH AF: 0.958

GnomAD4 exome AF: 0.955 AC: 1062597 AN: 1113042 Hom.: 507394 Cov.: 14 AF XY: 0.954 AC XY: 524402 AN XY: 549880

African (AFR) AF: 0.993 AC: 24081 AN: 24250

American (AMR) AF: 0.979 AC: 22185 AN: 22664

Ashkenazi Jewish (ASJ) AF: 0.934 AC: 16253 AN: 17410

East Asian (EAS) AF: 0.927 AC: 31555 AN: 34028

South Asian (SAS) AF: 0.928 AC: 47558 AN: 51274

European-Finnish (FIN) AF: 0.945 AC: 42430 AN: 44884

Middle Eastern (MID) AF: 0.921 AC: 4012 AN: 4358

European-Non Finnish (NFE) AF: 0.957 AC: 830160 AN: 867506

Other (OTH) AF: 0.951 AC: 44363 AN: 46668

GnomAD4 genome AF: 0.965 AC: 146851 AN: 152254 Hom.: 70836 Cov.: 31 AF XY: 0.963 AC XY: 71675 AN XY: 74456

African (AFR) AF: 0.992 AC: 41210 AN: 41532

American (AMR) AF: 0.966 AC: 14775 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.934 AC: 3243 AN: 3472

East Asian (EAS) AF: 0.923 AC: 4772 AN: 5172

South Asian (SAS) AF: 0.927 AC: 4468 AN: 4820

European-Finnish (FIN) AF: 0.952 AC: 10098 AN: 10610

Middle Eastern (MID) AF: 0.952 AC: 280 AN: 294

European-Non Finnish (NFE) AF: 0.957 AC: 65091 AN: 68032

Other (OTH) AF: 0.958 AC: 2026 AN: 2114

Alfa AF: 0.958 Hom.: 98756

Bravo AF: 0.967

Asia WGS AF: 0.931 AC: 3239 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Autosomal recessive limb-girdle muscular dystrophy type 2X (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.38
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs221657; hg19: chr6-105548850; COSMIC: COSV58949872;