1-145096983-G-C

Variant names:

• chr1-145096983-G-C
• rs1654491110
• NM_207418.3:c.136G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_207418.3(FAM72D):​c.136G>C​(p.Asp46His) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. 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. D46N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 14)
• Consequence: FAM72D NM_207418.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.72
• Publications: 0 publications found

Genes affected

FAM72D (HGNC:33593): (family with sequence similarity 72 member D) Located in cytosol and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.884

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207418.3. 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
	FAM72D	NM_207418.3	MANE Select	c.136G>C	p.Asp46His	missense	Exon 1 of 4	NP_997301.2
	FAM72D	NM_001345942.2		c.152+1954G>C		intron	N/A	NP_001332871.1
	FAM72D	NR_144320.2		n.327-2005G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM72D	ENST00000400889.3	TSL:1 MANE Select	c.136G>C	p.Asp46His	missense	Exon 1 of 4	ENSP00000383682.1	Q6L9T8
	FAM72D	ENST00000936347.1		c.32+104G>C		intron	N/A	ENSP00000606406.1

Frequencies

GnomAD3 genomes Cov.: 14

GnomAD4 exome Cov.: 13

GnomAD4 genome Cov.: 14

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	30
DEOGEN2	Benign	0.27	T
LIST_S2	Uncertain	0.91	D
MetaRNN	Pathogenic	0.88	D
PhyloP100		8.7
PROVEAN	Pathogenic	-6.4	D
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.92
gMVP		0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1654491110; hg19: chr1-143912160;