rs748520978

Variant names:

• chr6-70477264-C-G
• rs748520978
• NM_001162529.3:c.474C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-70477264-C-G
• chr6-70477264-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP6

The NM_001162529.3(FAM135A):​c.474C>G​(p.Tyr158*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM135A NM_001162529.3 stop_gained
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.157
• Publications: 1 publications found

Genes affected

FAM135A (HGNC:21084): (family with sequence similarity 135 member A) Predicted to be involved in cellular lipid metabolic process. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 6-70477264-C-G is Benign according to our data. Variant chr6-70477264-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 254142.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001162529.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM135A	NM_001162529.3	MANE Select	c.474C>G	p.Tyr158*	stop_gained	Exon 8 of 22	NP_001156001.1
	FAM135A	NM_001330996.3		c.474C>G	p.Tyr158*	stop_gained	Exon 7 of 22	NP_001317925.1
	FAM135A	NM_001330999.3		c.474C>G	p.Tyr158*	stop_gained	Exon 8 of 23	NP_001317928.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM135A	ENST00000418814.7	TSL:5 MANE Select	c.474C>G	p.Tyr158*	stop_gained	Exon 8 of 22	ENSP00000410768.2
	FAM135A	ENST00000370479.7	TSL:1	c.474C>G	p.Tyr158*	stop_gained	Exon 6 of 20	ENSP00000359510.4
	FAM135A	ENST00000361499.7	TSL:1	c.474C>G	p.Tyr158*	stop_gained	Exon 8 of 22	ENSP00000354913.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	Histiocytoid cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.45
CADD	Pathogenic	31
DANN	Uncertain	0.99
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.34
FATHMM_MKL	Uncertain	0.85	D
PhyloP100		0.16
Vest4		0.45
GERP RS		-4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=0/200	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs748520978; hg19: chr6-71186967;