NM_001174070.3:c.1171G>C

Variant names:

• chr4-1641319-C-G
• rs778363690
• NM_001174070.3:c.1171G>C

Variant summary

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

The NM_001174070.3(FAM53A):​c.1171G>C​(p.Asp391His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. D391N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM53A NM_001174070.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.98
• Publications: 0 publications found

Genes affected

FAM53A (HGNC:31860): (family with sequence similarity 53 member A) Predicted to be involved in protein import into nucleus. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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, 0.848

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001174070.3. 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
	FAM53A	NM_001174070.3	MANE Select	c.1171G>C	p.Asp391His	missense	Exon 5 of 5	NP_001167541.1	Q6NSI3
	FAM53A	NM_001013622.3		c.1171G>C	p.Asp391His	missense	Exon 5 of 5	NP_001013644.1	Q6NSI3
	FAM53A	NM_001297435.1		c.*242G>C		3_prime_UTR	Exon 6 of 6	NP_001284364.1	C9JYQ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM53A	ENST00000308132.11	TSL:2 MANE Select	c.1171G>C	p.Asp391His	missense	Exon 5 of 5	ENSP00000310057.6	Q6NSI3
	FAM53A	ENST00000472884.6	TSL:1	c.1171G>C	p.Asp391His	missense	Exon 5 of 5	ENSP00000426260.1	Q6NSI3
	FAM53A	ENST00000461064.5	TSL:2	c.1171G>C	p.Asp391His	missense	Exon 4 of 4	ENSP00000418243.1	Q6NSI3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.17
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.85	T
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	1.8	L
PhyloP100		5.0
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Uncertain	0.53
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.87
MutPred		0.51		Loss of helix (P = 0.0376)
MVP		0.64
MPC		0.51
ClinPred		1.0	D
GERP RS		3.8
Varity_R		0.89
gMVP		0.32
Mutation Taster		=89/11	polymorphism

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: rs778363690; hg19: chr4-1643046;