X-134807614-A-G

Variant names:

• chrX-134807614-A-G
• rs201369085
• NM_001388447.1:c.16A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001388447.1(PABIR3):​c.16A>G​(p.Met6Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 1,208,739 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.0000027 (0 hom. 1 hem.)
• Consequence: PABIR3 NM_001388447.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.64
• Publications: 0 publications found

Genes affected

PABIR3 (HGNC:25202): (PABIR family member 3) Predicted to enable protein serine/threonine phosphatase inhibitor activity. Predicted to be involved in negative regulation of catalytic activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11699957).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PABIR3	NM_001388447.1	c.16A>G	p.Met6Val	missense_variant	Exon 2 of 11	ENST00000645433.2	NP_001375376.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PABIR3	ENST00000645433.2	c.16A>G	p.Met6Val	missense_variant	Exon 2 of 11		NM_001388447.1	ENSP00000496338.1

Frequencies

GnomAD3 genomes AF: 0.0000179 AC: 2 AN: 111529 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000549 AC: 1 AN: 182060 AF XY: 0.00

Gnomad AFR exome AF: 0.0000763

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000273 AC: 3 AN: 1097157 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 1 AN XY: 362555

African (AFR) AF: 0.0000379 AC: 1 AN: 26388

American (AMR) AF: 0.00 AC: 0 AN: 35153

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19347

East Asian (EAS) AF: 0.00 AC: 0 AN: 30157

South Asian (SAS) AF: 0.00 AC: 0 AN: 53959

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40512

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4132

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841480

Other (OTH) AF: 0.0000217 AC: 1 AN: 46029

GnomAD4 genome AF: 0.0000179 AC: 2 AN: 111582 Hom.: 0 Cov.: 23 AF XY: 0.0000296 AC XY: 1 AN XY: 33800

African (AFR) AF: 0.0000651 AC: 2 AN: 30741

American (AMR) AF: 0.00 AC: 0 AN: 10488

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2644

East Asian (EAS) AF: 0.00 AC: 0 AN: 3562

South Asian (SAS) AF: 0.00 AC: 0 AN: 2662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6007

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53052

Other (OTH) AF: 0.00 AC: 0 AN: 1523

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.16A>G (p.M6V) alteration is located in exon 1 (coding exon 1) of the FAM122C gene. This alteration results from a A to G substitution at nucleotide position 16, causing the methionine (M) at amino acid position 6 to be replaced by a valine (V). 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	Benign	0.18
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	15
DANN	Benign	0.80
DEOGEN2	Benign	0.22	.;.;.;.;.;.;T;.;T;T;.;.
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.80	.;T;D;T;T;T;T;T;.;T;T;T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.12	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	2.0	.;.;.;.;.;.;M;M;.;.;.;.
PhyloP100		1.6
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.9	.;.;D;.;.;.;D;D;.;.;.;.
REVEL	Benign	0.16
Sift	Pathogenic	0.0	.;.;D;.;.;.;D;D;.;.;.;.
Sift4G	Pathogenic	0.0	.;.;D;.;.;D;D;D;.;.;.;.
Polyphen		0.27, 0.52	.;.;.;.;.;.;B;P;.;.;.;.
Vest4		0.40, 0.41, 0.45, 0.33
MVP		0.54
MPC		0.21
ClinPred		0.49	T
GERP RS		2.0
PromoterAI		0.32	Neutral
Varity_R		0.71
gMVP		0.44
Mutation Taster		=93/7	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: rs201369085; hg19: chrX-133941644;