11-773617-T-C

Variant names:

• chr11-773617-T-C
• rs373750262
• NM_182612.4:c.260A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_182612.4(GATD1):​c.260A>G​(p.His87Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000746 in 1,607,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: GATD1 NM_182612.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.06
• Publications: 1 publications found

Genes affected

GATD1 (HGNC:26616): (glutamine amidotransferase class 1 domain containing 1) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32930267).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182612.4. 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
	GATD1	NM_182612.4	MANE Select	c.260A>G	p.His87Arg	missense	Exon 4 of 8	NP_872418.1	Q8NB37-1
	GATD1	NM_001318821.2		c.260A>G	p.His87Arg	missense	Exon 4 of 7	NP_001305750.1
	GATD1	NM_001410955.1		c.260A>G	p.His87Arg	missense	Exon 4 of 7	NP_001397884.1	E9PLI5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATD1	ENST00000319863.13	TSL:1 MANE Select	c.260A>G	p.His87Arg	missense	Exon 4 of 8	ENSP00000321691.8	Q8NB37-1
	GATD1	ENST00000397472.6	TSL:1	c.260A>G	p.His87Arg	missense	Exon 4 of 8	ENSP00000380612.2	Q8NB37-2
	GATD1	ENST00000524550.5	TSL:1	c.247+391A>G		intron	N/A	ENSP00000431183.1	Q8NB37-3

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152074 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000166 AC: 4 AN: 240448 AF XY: 0.0000229

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000368

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000756 AC: 11 AN: 1455900 Hom.: 0 Cov.: 31 AF XY: 0.00000552 AC XY: 4 AN XY: 724220

African (AFR) AF: 0.00 AC: 0 AN: 33194

American (AMR) AF: 0.00 AC: 0 AN: 43208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25856

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.00 AC: 0 AN: 85590

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00000811 AC: 9 AN: 1110396

Other (OTH) AF: 0.0000333 AC: 2 AN: 60114

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152074 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74278

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41406

American (AMR) AF: 0.00 AC: 0 AN: 15268

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67974

Other (OTH) AF: 0.00 AC: 0 AN: 2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000508 Hom.: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000248 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	0.0084	T
BayesDel_noAF	Benign	-0.090
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.039	T
Eigen	Benign	0.067
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.33	T
MetaSVM	Uncertain	-0.23	T
PhyloP100		5.1
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.58
Sift	Benign	0.31	T
Sift4G	Benign	0.079	T
Polyphen		0.59	P
Vest4		0.61
MVP		0.31
MPC		0.42
ClinPred		0.17	T
GERP RS		4.6
PromoterAI		0.017	Neutral
Varity_R		0.26
gMVP		0.56
Mutation Taster		=61/39	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: rs373750262; hg19: chr11-773617;