rs1235105622

Variant names:

• chr9-131261298-C-A
• rs1235105622
• NM_033387.4:c.376G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-131261298-C-A
• chr9-131261298-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_033387.4(FAM78A):​c.376G>T​(p.Asp126Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,132 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D126N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FAM78A NM_033387.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.84
• Publications: 0 publications found

Genes affected

FAM78A (HGNC:25465): (family with sequence similarity 78 member A)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.915

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033387.4. 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
	FAM78A	NM_033387.4	MANE Select	c.376G>T	p.Asp126Tyr	missense	Exon 2 of 2	NP_203745.2	Q5JUQ0
	FAM78A	NM_001399459.1		c.376G>T	p.Asp126Tyr	missense	Exon 3 of 3	NP_001386388.1	Q5JUQ0
	FAM78A	NM_001400581.1		c.376G>T	p.Asp126Tyr	missense	Exon 3 of 3	NP_001387510.1	Q5JUQ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM78A	ENST00000372271.4	TSL:1 MANE Select	c.376G>T	p.Asp126Tyr	missense	Exon 2 of 2	ENSP00000361345.3	Q5JUQ0
	FAM78A	ENST00000372269.7	TSL:1	c.367G>T	p.Asp123Tyr	missense	Exon 4 of 4	ENSP00000361343.3	Q5JUQ2
	FAM78A	ENST00000704762.1		c.376G>T	p.Asp126Tyr	missense	Exon 3 of 3	ENSP00000516028.1	Q5JUQ0

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1452132 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 722632

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25984

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45044

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111190

Other (OTH) AF: 0.00 AC: 0 AN: 60272

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.45	D
BayesDel_noAF	Pathogenic	0.41
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.50	T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.026	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	-0.061	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.8
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-6.0	D
REVEL	Pathogenic	0.83
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.96
MutPred		0.78		Loss of disorder (P = 0.0441)
MVP		0.17
MPC		2.0
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.83
gMVP		0.93
Mutation Taster		=27/73	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs1235105622; hg19: chr9-134136685;