9-34399340-A-G

Variant names:

• chr9-34399340-A-G
• rs885048
• NM_001184940.2:c.*1624T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001184940.2(FAM219A):​c.*1624T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 151,820 control chromosomes in the GnomAD database, including 1,559 homozygotes. 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: 𝑓 0.13 (1557 hom., cov: 31)
  • Exomes 𝑓: 0.13 (2 hom.)
• Consequence: FAM219A NM_001184940.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163
• Publications: 9 publications found

Genes affected

FAM219A (HGNC:19920): (family with sequence similarity 219 member A) The protein encoded by this gene has homologs that have been identified in mouse, macaque, etc organisms. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM219A	NM_001184940.2	c.*1624T>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000651358.1	NP_001171869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM219A	ENST00000651358.1	c.*1624T>C		3_prime_UTR_variant	Exon 6 of 6		NM_001184940.2	ENSP00000499069.1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18962 AN: 151486 Hom.: 1557 Cov.: 31

Gnomad AFR AF: 0.0337

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.00601

Gnomad SAS AF: 0.0607

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.127

GnomAD4 exome AF: 0.130 AC: 28 AN: 216 Hom.: 2 Cov.: 0 AF XY: 0.132 AC XY: 23 AN XY: 174

African (AFR) AF: 0.00 AC: 0 AN: 6

American (AMR) AF: 0.500 AC: 2 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

European-Finnish (FIN) AF: 0.143 AC: 2 AN: 14

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.130 AC: 21 AN: 162

Other (OTH) AF: 0.0909 AC: 2 AN: 22

GnomAD4 genome AF: 0.125 AC: 18955 AN: 151604 Hom.: 1557 Cov.: 31 AF XY: 0.122 AC XY: 9058 AN XY: 74074

African (AFR) AF: 0.0336 AC: 1387 AN: 41260

American (AMR) AF: 0.133 AC: 2022 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 606 AN: 3468

East Asian (EAS) AF: 0.00583 AC: 30 AN: 5144

South Asian (SAS) AF: 0.0603 AC: 289 AN: 4792

European-Finnish (FIN) AF: 0.188 AC: 1986 AN: 10538

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12183 AN: 67846

Other (OTH) AF: 0.125 AC: 263 AN: 2108

Alfa AF: 0.159 Hom.: 2650

Bravo AF: 0.116

Asia WGS AF: 0.0310 AC: 112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.47
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

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: rs885048; hg19: chr9-34399338;