chr19-16185764-G-T

Variant names:

• chr19-16185764-G-T
• rs752589613
• NM_014077.4:c.215G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014077.4(FAM32A):​c.215G>T​(p.Arg72Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000452 in 1,549,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R72W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000047 (0 hom.)
• Consequence: FAM32A NM_014077.4 missense, splice_region
• Scores: Splicing: ADA: 0.8783
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.73
• Publications: 1 publications found

Genes affected

FAM32A (HGNC:24563): (family with sequence similarity 32 member A) Enables RNA binding activity. Predicted to be involved in apoptotic process. Located in nucleolus and nucleoplasm. [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
• BP4: Computational evidence support a benign effect (MetaRNN=0.39933512).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014077.4. 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
	FAM32A	NM_014077.4	MANE Select	c.215G>T	p.Arg72Leu	missense splice_region	Exon 2 of 4	NP_054796.1	Q9Y421-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM32A	ENST00000263384.12	TSL:1 MANE Select	c.215G>T	p.Arg72Leu	missense splice_region	Exon 2 of 4	ENSP00000263384.6	Q9Y421-1
	FAM32A	ENST00000589852.5	TSL:1	c.155G>T	p.Arg52Leu	missense splice_region	Exon 1 of 3	ENSP00000465969.1	Q9Y421-3
	FAM32A	ENST00000921004.1		c.215G>T	p.Arg72Leu	missense splice_region	Exon 2 of 4	ENSP00000591063.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152240 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000131 AC: 2 AN: 152740 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: 0.0000338

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000472 AC: 66 AN: 1397204 Hom.: 0 Cov.: 31 AF XY: 0.0000493 AC XY: 34 AN XY: 689324

African (AFR) AF: 0.0000319 AC: 1 AN: 31328

American (AMR) AF: 0.00 AC: 0 AN: 34742

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25102

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49218

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5608

European-Non Finnish (NFE) AF: 0.0000575 AC: 62 AN: 1078392

Other (OTH) AF: 0.0000346 AC: 2 AN: 57876

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152240 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74376

African (AFR) AF: 0.0000241 AC: 1 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000674 Hom.: 0

Bravo AF: 0.0000227

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
PhyloP100		6.7
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.20
Sift	Benign	0.066	T
Sift4G	Benign	0.31	T
Polyphen		0.60	P
Vest4		0.74
MVP		0.21
MPC		1.5
ClinPred		0.95	D
GERP RS		3.3
PromoterAI		0.011	Neutral
Varity_R		0.64
gMVP		0.88
Mutation Taster		=58/42	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.88
dbscSNV1_RF	Pathogenic	0.81
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: rs752589613; hg19: chr19-16296575;