chr7-135737101-C-G

Variant names:

• chr7-135737101-C-G
• rs890848627
• NM_205855.4:c.175G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_205855.4(FAM180A):​c.175G>C​(p.Glu59Gln) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000686 in 1,458,022 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E59K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FAM180A NM_205855.4 missense, splice_region
• Scores: Splicing: ADA: 0.02397
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.58
• Publications: 0 publications found

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]

ENSG00000299635 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_205855.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM180A	NM_205855.4	MANE Select	c.175G>C	p.Glu59Gln	missense splice_region	Exon 2 of 4	NP_995327.1	Q6UWF9
	FAM180A	NM_001369697.2		c.175G>C	p.Glu59Gln	missense splice_region	Exon 2 of 3	NP_001356626.1	Q6UWF9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM180A	ENST00000338588.8	TSL:1 MANE Select	c.175G>C	p.Glu59Gln	missense splice_region	Exon 2 of 4	ENSP00000342336.3	Q6UWF9
	FAM180A	ENST00000435869.1	TSL:1	n.408G>C		splice_region non_coding_transcript_exon	Exon 2 of 3
	FAM180A	ENST00000444083.5	TSL:1	n.175G>C		splice_region non_coding_transcript_exon	Exon 2 of 4	ENSP00000406553.1	Q6UWF9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458022 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725248

African (AFR) AF: 0.00 AC: 0 AN: 33404

American (AMR) AF: 0.00 AC: 0 AN: 44486

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26036

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 85604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109484

Other (OTH) AF: 0.00 AC: 0 AN: 60264

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	-0.0099	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	2.0	M
PhyloP100		4.6
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.27
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.97	D
Vest4		0.64
MutPred		0.41		Loss of disorder (P = 0.1761)
MVP		0.36
MPC		0.22
ClinPred		0.99	D
GERP RS		4.3
Varity_R		0.68
gMVP		0.72
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.024
dbscSNV1_RF	Benign	0.37
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: rs890848627; hg19: chr7-135421849;