chr5-58494776-C-T

Variant names:

• chr5-58494776-C-T
• rs35272273
• NM_001304431.2:c.240C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001304431.2(GAPT):​c.240C>T​(p.His80His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00311 in 1,613,914 control chromosomes in the GnomAD database, including 117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (59 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (58 hom.)
• Consequence: GAPT NM_001304431.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.04
• Publications: 2 publications found

Genes affected

GAPT (HGNC:26588): (GRB2 binding adaptor protein, transmembrane) Predicted to be involved in B cell homeostasis and B cell proliferation involved in immune response. Located in Golgi apparatus and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 5-58494776-C-T is Benign according to our data. Variant chr5-58494776-C-T is described in ClinVar as Benign. ClinVar VariationId is 785125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.04 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.054 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001304431.2. 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
	GAPT	NM_001304431.2	MANE Select	c.240C>T	p.His80His	synonymous	Exon 3 of 3	NP_001291360.1	Q8N292
	GAPT	NM_001304428.2		c.240C>T	p.His80His	synonymous	Exon 3 of 3	NP_001291357.1	Q8N292
	GAPT	NM_001304429.2		c.240C>T	p.His80His	synonymous	Exon 3 of 3	NP_001291358.1	Q8N292

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAPT	ENST00000502276.6	TSL:4 MANE Select	c.240C>T	p.His80His	synonymous	Exon 3 of 3	ENSP00000423113.2	Q8N292
	GAPT	ENST00000318469.2	TSL:6	c.240C>T	p.His80His	synonymous	Exon 1 of 1	ENSP00000323075.2	Q8N292
	GAPT	ENST00000396776.6	TSL:2	c.240C>T	p.His80His	synonymous	Exon 3 of 3	ENSP00000379997.2	Q8N292

Frequencies

GnomAD3 genomes AF: 0.0164 AC: 2495 AN: 152124 Hom.: 58 Cov.: 32

Gnomad AFR AF: 0.0560

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00773

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.00424 AC: 1062 AN: 250586 AF XY: 0.00322

Gnomad AFR exome AF: 0.0553

Gnomad AMR exome AF: 0.00342

Gnomad ASJ exome AF: 0.0000995

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000248

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.00172 AC: 2517 AN: 1461672 Hom.: 58 Cov.: 32 AF XY: 0.00149 AC XY: 1087 AN XY: 727124

African (AFR) AF: 0.0566 AC: 1894 AN: 33474

American (AMR) AF: 0.00336 AC: 150 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.000359 AC: 31 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53404

Middle Eastern (MID) AF: 0.00312 AC: 18 AN: 5764

European-Non Finnish (NFE) AF: 0.000165 AC: 184 AN: 1111920

Other (OTH) AF: 0.00396 AC: 239 AN: 60392

GnomAD4 genome AF: 0.0164 AC: 2499 AN: 152242 Hom.: 59 Cov.: 32 AF XY: 0.0160 AC XY: 1188 AN XY: 74426

African (AFR) AF: 0.0559 AC: 2321 AN: 41522

American (AMR) AF: 0.00772 AC: 118 AN: 15294

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 68026

Other (OTH) AF: 0.0147 AC: 31 AN: 2116

Alfa AF: 0.00551 Hom.: 15

Bravo AF: 0.0184

Asia WGS AF: 0.00376 AC: 13 AN: 3476

EpiCase AF: 0.000382

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.44
PhyloP100		1.0
Mutation Taster		=99/1	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: rs35272273; hg19: chr5-57790603;