7-128677617-T-C

Variant names:

• chr7-128677617-T-C
• NM_001128926.4:c.392T>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001128926.4(GARIN1A):​c.392T>C​(p.Ile131Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GARIN1A NM_001128926.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.98

Genes affected

GARIN1A (HGNC:27998): (golgi associated RAB2 interactor 1A)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36844563).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GARIN1A	NM_001128926.4	c.392T>C	p.Ile131Thr	missense_variant	Exon 3 of 5	ENST00000682356.1	NP_001122398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GARIN1A	ENST00000682356.1	c.392T>C	p.Ile131Thr	missense_variant	Exon 3 of 5		NM_001128926.4	ENSP00000506740.1
GARIN1A	ENST00000641605.1	c.419T>C	p.Ile140Thr	missense_variant	Exon 3 of 5			ENSP00000493102.1
GARIN1A	ENST00000477515.3	c.365+1758T>C		intron_variant	Intron 2 of 3	1		ENSP00000419649.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457840 Hom.: 0 Cov.: 38 AF XY: 0.00000138 AC XY: 1 AN XY: 725168

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.419T>C (p.I140T) alteration is located in exon 3 (coding exon 3) of the FAM71F2 gene. This alteration results from a T to C substitution at nucleotide position 419, causing the isoleucine (I) at amino acid position 140 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.067	T;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.37	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.0	M;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.38	.;N
REVEL	Benign	0.11
Sift	Benign	0.28	.;T
Sift4G	Uncertain	0.049	.;D
Polyphen		0.98	D;D
MutPred		0.51		Loss of stability (P = 0.0022);.;
ClinPred		0.85	D
GERP RS		5.6
Varity_R		0.46
gMVP		0.28

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-128317671;