7-135748524-C-G

Variant names:

• chr7-135748524-C-G
• NM_205855.4:c.57G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_205855.4(FAM180A):​c.57G>C​(p.Met19Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM180A NM_205855.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.799

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039629906).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM180A	NM_205855.4	c.57G>C	p.Met19Ile	missense_variant	Exon 1 of 4	ENST00000338588.8	NP_995327.1
FAM180A	NM_001369697.2	c.57G>C	p.Met19Ile	missense_variant	Exon 1 of 3		NP_001356626.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM180A	ENST00000338588.8	c.57G>C	p.Met19Ile	missense_variant	Exon 1 of 4	1	NM_205855.4	ENSP00000342336.3
FAM180A	ENST00000435869.1	n.290G>C		non_coding_transcript_exon_variant	Exon 1 of 3	1
FAM180A	ENST00000444083.5	n.57G>C		non_coding_transcript_exon_variant	Exon 1 of 4	1		ENSP00000406553.1
FAM180A	ENST00000415751.1	c.57G>C	p.Met19Ile	missense_variant	Exon 1 of 3	2		ENSP00000395467.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.57G>C (p.M19I) alteration is located in exon 1 (coding exon 1) of the FAM180A gene. This alteration results from a G to C substitution at nucleotide position 57, causing the methionine (M) at amino acid position 19 to be replaced by an isoleucine (I). 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	0.10
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.34
DEOGEN2	Benign	0.0015	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.48	T;.
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.040	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.69	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.31	N;N
REVEL	Benign	0.085
Sift	Benign	0.53	T;T
Sift4G	Benign	0.67	T;T
Polyphen		0.0	B;B
Vest4		0.12
MutPred		0.27		Loss of MoRF binding (P = 0.0865);Loss of MoRF binding (P = 0.0865);
MVP		0.040
MPC		0.11
ClinPred		0.049	T
GERP RS		4.3
Varity_R		0.16
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr7-135433272;