2-131052938-T-C

Variant names:

• chr2-131052938-T-C
• NM_001009993.4:c.553A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001009993.4(FAM168B):​c.553A>G​(p.Thr185Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T185M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM168B NM_001009993.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.59

Genes affected

FAM168B (HGNC:27016): (family with sequence similarity 168 member B) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM168B	NM_001009993.4	c.553A>G	p.Thr185Ala	missense_variant	Exon 6 of 7	ENST00000389915.4	NP_001009993.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM168B	ENST00000389915.4	c.553A>G	p.Thr185Ala	missense_variant	Exon 6 of 7	3	NM_001009993.4	ENSP00000374565.3
FAM168B	ENST00000409185.5	c.553A>G	p.Thr185Ala	missense_variant	Exon 6 of 7	1		ENSP00000387051.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1411644 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 697366

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.553A>G (p.T185A) alteration is located in exon 6 (coding exon 5) of the FAM168B gene. This alteration results from a A to G substitution at nucleotide position 553, causing the threonine (T) at amino acid position 185 to be replaced by an alanine (A). 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	0.11
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.084	T;T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.81	.;T
M_CAP	Benign	0.0050	T
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.1	N;N
REVEL	Uncertain	0.29
Sift	Benign	0.049	D;D
Sift4G	Benign	0.30	T;T
Polyphen		0.97	D;D
Vest4		0.76
MutPred		0.17		Loss of glycosylation at T185 (P = 0.0218);Loss of glycosylation at T185 (P = 0.0218);
MVP		0.28
MPC		0.67
ClinPred		0.83	D
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.20
gMVP		0.67

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: chr2-131810511;