rs7541937

Variant names:

• chr1-34876381-T-G
• rs7541937
• NM_001080418.3:c.2001-7292A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080418.3(DLGAP3):​c.2001-7292A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 151,952 control chromosomes in the GnomAD database, including 16,919 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (16919 hom., cov: 33)
• Consequence: DLGAP3 NM_001080418.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.261
• Publications: 8 publications found

Genes affected

DLGAP3 (HGNC:30368): (DLG associated protein 3) Predicted to enable PDZ domain binding activity; molecular adaptor activity; and scaffold protein binding activity. Predicted to be involved in protein-containing complex assembly and regulation of postsynaptic neurotransmitter receptor activity. Predicted to be located in synapse. Predicted to be part of postsynaptic density. Predicted to be active in several cellular components, including cholinergic synapse; glutamatergic synapse; and neuromuscular junction. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP3	NM_001080418.3	c.2001-7292A>C		intron_variant	Intron 8 of 11	ENST00000373347.6	NP_001073887.1
DLGAP3	XM_011541879.3	c.2001-7292A>C		intron_variant	Intron 9 of 12		XP_011540181.1
DLGAP3	XM_047426631.1	c.2001-7292A>C		intron_variant	Intron 8 of 11		XP_047282587.1
DLGAP3	XM_011541880.3	c.510-7292A>C		intron_variant	Intron 4 of 7		XP_011540182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLGAP3	ENST00000373347.6	c.2001-7292A>C		intron_variant	Intron 8 of 11	5	NM_001080418.3	ENSP00000362444.1
DLGAP3	ENST00000235180.4	c.2001-7292A>C		intron_variant	Intron 6 of 9	2		ENSP00000235180.4

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70242 AN: 151834 Hom.: 16913 Cov.: 33

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.0410

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.450

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.462 AC: 70269 AN: 151952 Hom.: 16919 Cov.: 33 AF XY: 0.448 AC XY: 33259 AN XY: 74274

African (AFR) AF: 0.464 AC: 19246 AN: 41458

American (AMR) AF: 0.403 AC: 6152 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1532 AN: 3468

East Asian (EAS) AF: 0.0407 AC: 210 AN: 5160

South Asian (SAS) AF: 0.375 AC: 1809 AN: 4822

European-Finnish (FIN) AF: 0.380 AC: 4003 AN: 10536

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.525 AC: 35686 AN: 67924

Other (OTH) AF: 0.447 AC: 944 AN: 2110

Alfa AF: 0.509 Hom.: 32883

Bravo AF: 0.465

Asia WGS AF: 0.256 AC: 895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.3
DANN	Benign	0.58
PhyloP100		0.26
Mutation Taster		=100/0	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: rs7541937; hg19: chr1-35341982;