1-34905250-G-T

Variant names:

• chr1-34905250-G-T
• rs552097335
• NM_001080418.3:c.134C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001080418.3(DLGAP3):​c.134C>A​(p.Pro45His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,593,864 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P45T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (2 hom.)
• Consequence: DLGAP3 NM_001080418.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.22
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005319208).
• BP6: Variant 1-34905250-G-T is Benign according to our data. Variant chr1-34905250-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 722225.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP3	NM_001080418.3	c.134C>A	p.Pro45His	missense_variant	Exon 3 of 12	ENST00000373347.6	NP_001073887.1
DLGAP3	XM_011541879.3	c.134C>A	p.Pro45His	missense_variant	Exon 4 of 13		XP_011540181.1
DLGAP3	XM_047426631.1	c.134C>A	p.Pro45His	missense_variant	Exon 3 of 12		XP_047282587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLGAP3	ENST00000373347.6	c.134C>A	p.Pro45His	missense_variant	Exon 3 of 12	5	NM_001080418.3	ENSP00000362444.1
DLGAP3	ENST00000235180.4	c.134C>A	p.Pro45His	missense_variant	Exon 1 of 10	2		ENSP00000235180.4
DLGAP3	ENST00000495979.1	n.389C>A		non_coding_transcript_exon_variant	Exon 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00444

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000305 AC: 63 AN: 206576 AF XY: 0.000347

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000652

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00374

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000110 AC: 158 AN: 1441544 Hom.: 2 Cov.: 33 AF XY: 0.000103 AC XY: 74 AN XY: 714976

African (AFR) AF: 0.00 AC: 0 AN: 33206

American (AMR) AF: 0.0000479 AC: 2 AN: 41726

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25536

East Asian (EAS) AF: 0.00295 AC: 115 AN: 38954

South Asian (SAS) AF: 0.0000121 AC: 1 AN: 82616

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51728

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5500

European-Non Finnish (NFE) AF: 9.07e-7 AC: 1 AN: 1102682

Other (OTH) AF: 0.000654 AC: 39 AN: 59596

GnomAD4 genome AF: 0.000184 AC: 28 AN: 152320 Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12 AN XY: 74482

African (AFR) AF: 0.00 AC: 0 AN: 41580

American (AMR) AF: 0.0000653 AC: 1 AN: 15308

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

East Asian (EAS) AF: 0.00445 AC: 23 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000223

ExAC AF: 0.000232 AC: 28

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 17, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	20
DANN	Benign	0.75
DEOGEN2	Benign	0.027	T;T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.58	T;.
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.0053	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.17	N;N
PhyloP100		1.2
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	1.5	N;N
REVEL	Benign	0.037
Sift	Benign	0.53	T;T
Sift4G	Benign	0.69	T;T
Polyphen		0.0060	B;B
Vest4		0.25
MutPred		0.27		Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP		0.14
MPC		0.68
ClinPred		0.012	T
GERP RS		3.5
PromoterAI		0.0060	Neutral
Varity_R		0.078
gMVP		0.30
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: rs552097335; hg19: chr1-35370851;