7-135734094-A-G

Variant names:

• chr7-135734094-A-G
• rs1796835180
• NM_205855.4:c.403T>C

Variant summary

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

The NM_205855.4(FAM180A):​c.403T>C​(p.Tyr135His) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,864 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: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FAM180A NM_205855.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.30

Genes affected

FAM180A (HGNC:33773): (family with sequence similarity 180 member A) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

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=0.3863238).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM180A	NM_205855.4	c.403T>C	p.Tyr135His	missense_variant	Exon 3 of 4	ENST00000338588.8	NP_995327.1
FAM180A	NM_001369697.2	c.403T>C	p.Tyr135His	missense_variant	Exon 3 of 3		NP_001356626.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM180A	ENST00000338588.8	c.403T>C	p.Tyr135His	missense_variant	Exon 3 of 4	1	NM_205855.4	ENSP00000342336.3
FAM180A	ENST00000444083.5	n.403T>C		non_coding_transcript_exon_variant	Exon 3 of 4	1		ENSP00000406553.1
FAM180A	ENST00000435869.1	n.410+3005T>C		intron_variant	Intron 2 of 2	1
FAM180A	ENST00000415751.1	c.403T>C	p.Tyr135His	missense_variant	Exon 3 of 3	2		ENSP00000395467.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461864 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727230

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 18, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.403T>C (p.Y135H) alteration is located in exon 3 (coding exon 3) of the FAM180A gene. This alteration results from a T to C substitution at nucleotide position 403, causing the tyrosine (Y) at amino acid position 135 to be replaced by a histidine (H). 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	0.30
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.056	T;T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.81	T;.
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.0	M;M
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.2	N;N
REVEL	Benign	0.16
Sift	Benign	0.25	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.55	P;P
Vest4		0.61
MutPred		0.53		Gain of disorder (P = 0.0413);Gain of disorder (P = 0.0413);
MVP		0.14
MPC		0.58
ClinPred		0.78	D
GERP RS		5.7
Varity_R		0.13
gMVP		0.58

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

LitVar

Other links and lift over

dbSNP: rs1796835180; hg19: chr7-135418842;