17-44353915-G-A

Variant names:

• chr17-44353915-G-A
• NM_198475.3:c.2299C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198475.3(FAM171A2):​c.2299C>T​(p.Pro767Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000697 in 1,148,224 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: 0.0000070 (0 hom.)
• Consequence: FAM171A2 NM_198475.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.92

Genes affected

FAM171A2 (HGNC:30480): (family with sequence similarity 171 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16618258).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM171A2	NM_198475.3	c.2299C>T	p.Pro767Ser	missense_variant	Exon 8 of 8	ENST00000293443.12	NP_940877.2
FAM171A2	XM_017024490.2	c.1747C>T	p.Pro583Ser	missense_variant	Exon 6 of 6		XP_016879979.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM171A2	ENST00000293443.12	c.2299C>T	p.Pro767Ser	missense_variant	Exon 8 of 8	1	NM_198475.3	ENSP00000293443.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000697 AC: 8 AN: 1148224 Hom.: 0 Cov.: 30 AF XY: 0.0000108 AC XY: 6 AN XY: 556868

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: 0.00000831

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

May 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2299C>T (p.P767S) alteration is located in exon 8 (coding exon 8) of the FAM171A2 gene. This alteration results from a C to T substitution at nucleotide position 2299, causing the proline (P) at amino acid position 767 to be replaced by a serine (S). 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	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Uncertain	25
DANN	Benign	0.95
DEOGEN2	Benign	0.0070	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.53	T
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.078
Sift	Benign	0.12	T
Sift4G	Uncertain	0.033	D
Polyphen		0.026	B
Vest4		0.081
MutPred		0.44		Gain of phosphorylation at P767 (P = 0.0027);
MVP		0.040
ClinPred		0.63	D
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.093
gMVP		0.44

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: chr17-42431283;