10-59247701-A-G

Variant names:

• chr10-59247701-A-G
• rs375423061
• NM_198215.4:c.1671T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_198215.4(FAM13C):​c.1671T>C​(p.Asp557Asp) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM13C NM_198215.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160
• Publications: 0 publications found

Genes affected

FAM13C (HGNC:19371): (family with sequence similarity 13 member C)

PHYHIPL (HGNC:29378): (phytanoyl-CoA 2-hydroxylase interacting protein like) Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=-0.016 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198215.4. 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
	FAM13C	NM_198215.4	MANE Select	c.1671T>C	p.Asp557Asp	synonymous	Exon 14 of 14	NP_937858.2	Q8NE31-1
	PHYHIPL	NM_032439.4	MANE Select	c.*2110A>G		3_prime_UTR	Exon 5 of 5	NP_115815.2	Q96FC7-1
	FAM13C	NM_001143773.1		c.1422T>C	p.Asp474Asp	synonymous	Exon 15 of 15	NP_001137245.1	B4DSU7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM13C	ENST00000618804.5	TSL:1 MANE Select	c.1671T>C	p.Asp557Asp	synonymous	Exon 14 of 14	ENSP00000481854.1	Q8NE31-1
	FAM13C	ENST00000611933.4	TSL:1	c.1377T>C	p.Asp459Asp	synonymous	Exon 12 of 12	ENSP00000481830.1	Q8NE31-3
	PHYHIPL	ENST00000373880.9	TSL:1 MANE Select	c.*2110A>G		3_prime_UTR	Exon 5 of 5	ENSP00000362987.4	Q96FC7-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250758 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	3.6
DANN	Benign	0.80
PhyloP100		-0.016

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs375423061; hg19: chr10-61007461;