11-774014-T-C

Variant names:

• chr11-774014-T-C
• rs370249003
• NM_182612.4:c.241A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182612.4(GATD1):​c.241A>G​(p.Ile81Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I81F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: GATD1 NM_182612.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.72
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10211107).

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.241A>G	p.Ile81Val	missense	Exon 3 of 8	NP_872418.1	Q8NB37-1
	GATD1	NM_001318821.2		c.241A>G	p.Ile81Val	missense	Exon 3 of 7	NP_001305750.1
	GATD1	NM_001410955.1		c.241A>G	p.Ile81Val	missense	Exon 3 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.241A>G	p.Ile81Val	missense	Exon 3 of 8	ENSP00000321691.8	Q8NB37-1
	GATD1	ENST00000397472.6	TSL:1	c.241A>G	p.Ile81Val	missense	Exon 3 of 8	ENSP00000380612.2	Q8NB37-2
	GATD1	ENST00000524550.5	TSL:1	c.241A>G	p.Ile81Val	missense	Exon 3 of 7	ENSP00000431183.1	Q8NB37-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461282 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726946

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111954

Other (OTH) AF: 0.0000166 AC: 1 AN: 60380

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	15
DANN	Benign	0.66
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.95	T
PhyloP100		2.7
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	0.080	N
REVEL	Benign	0.20
Sift	Benign	1.0	T
Sift4G	Benign	0.46	T
Polyphen		0.066	B
Vest4		0.40
MutPred		0.44		Gain of sheet (P = 0.0344)
MVP		0.12
MPC		0.22
ClinPred		0.23	T
GERP RS		4.6
PromoterAI		-0.027	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.041
gMVP		0.34
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs370249003; hg19: chr11-774014;